The Effects of Cannabis (Marijuana) on the Brain & Body | Huberman Lab Podcast #92

- Welcome to the Huberman Lab Podcast.

where we discuss science and science-based tools

for everyday life.

[bright music]

I'm Andrew Huberman, and I'm a professor of neurobiology

and ophthalmology at Stanford School of Medicine.

Today, we are discussing cannabis,

also referred to as marijuana.

Cannabis includes many different compounds

that have profound impact on the brain and body,

so while many of you have probably heard of THC,

there are also compounds in cannabis such as CBD,

and of course there are different types

or strains of cannabis,

including sativa strains and indica strains

and hybrid strains, and believe it or not,

nowadays, there is also an entire literature,

meaning a scientific and medicinal literature

about type one, type two and type three strains.

I'll explain what all of that is and how they work.

I'll talk about some of the medicinal applications

of different strains of cannabis

and combinations of cannabis strains,

as well as some of the potential health hazards

of cannabis use.

I want to emphasize that any discussion about cannabis

has to be framed within the context

that the legality of cannabis varies tremendously

depending on where you are in the world,

so depending on which country you're in

and even which state you're in

or which area within a country,

possessing and using and certainly selling cannabis

can be either highly illegal or entirely legal

or decriminalized or largely overlooked.

You, of course, are obligated to know

what those local laws are for you,

where you live and where you travel.

With that said, today's discussion

really will include a full picture

as to where cannabis and the various

and even very specific compounds within cannabis

can be extremely useful in the treatment of some ailments

and where certain compounds in cannabis

can be extremely dangerous for certain individuals to use,

in particular, individuals that have preexisting,

genetic propensity for psychosis.

That theme is going to come up again and again,

but we are also going to talk about the role of cannabis

in anxiety and depression,

both positive and negative effects.

We'll talk about sex differences

in terms of women versus men

and how they react differently to cannabis,

and I would be entirely remiss

if I didn't include a conversation about cannabis,

meaning THC, CBD, hybrid strains, et cetera

in creativity and different modes of thinking,

because as many of you probably know

or at least have heard about,

cannabis can impact the way that we think,

the types of memory systems we can access

and what's called convergent and divergent thinking,

which is one way of conceptualizing

what is commonly referred to as creativity.

So today's discussion is going to include

a lot of information,

but I promise to make it clear and accessible to all of you,

regardless of whether or not you have a background

in biology or not,

and today's discussion will also be quite nuanced.

You'll find me routinely reading

directly from specific research papers,

something that of course we always do on this podcast,

but today I'm really going to dig

into some of the finer points of the methodology in papers

and some of the statistics that were used

and the specific populations of people that were studied,

because as it turns out,

there are instances that we will discuss

in which the use of cannabis can be immensely beneficial

to one group and yet can be entirely detrimental

to another group, even at equivalent dosages

and depending on a number of different factors,

so we will discuss what those factors are.

Just to give you a brief overview

of the kind of structure I'm going to put on today's episode,

we will review of course, cannabis and its various forms.

I'll talk about some of the biology,

but we are going to really drill into how dosage,

that is the concentration of THC relative to CBD,

impacts whether or not cannabis

is going to have one effect or another.

We will also talk about the frequency of use,

daily use, multiple times per day use,

weekly use or monthly or occasional use.

We will also talk about different professions

and how some people may have a little bit more leeway

in terms of whether or not they decide to use cannabis

or any of its various component chemical constituents,

that is CBD or THC, et cetera.

And for other professions,

it might be entirely inappropriate

because of the particular kinds of cognitive tasks

those professions demand.

We will also talk about genetic predisposition,

again, sex differences, hormone effects,

and I will also touch on what I think

is the most important variable

in determining whether or not cannabis

is right or wrong for you, and that is your age

at which you are considering starting

or continuing use or ceasing use.

What I can assure you is that by the end of today's podcast,

you will have a quite thorough understanding of cannabis,

how it works, what it does,

what its potential benefits can be,

what its potential hazards are,

and whether or not it's right for you

and the people that you know.

I'm excited to announce that the Huberman Lab Podcast

has now launched a premium channel.

The purpose of the premium channel is severalfold.

First of all, I will be hosting regular AMAs,

Ask Me Anythings, where you can ask me anything,

and I will provide answers in depth

to your specific questions about science

and science related tools for mental health,

physical health and performance.

Now, there is a nominal cost to the premium channel.

It's $10 per month, or you can pay $100 for the entire year.

I should mention, however,

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so not animal models, but on human beings,

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And, we are going to specifically fund research

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whatever funds come in through the premium channel

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If you'd like to sign up

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Before diving into all of that, I'd like to highlight a new,

what I think is a very useful and zero cost resource.

This resource is what's called Non-Sleep Deep Rest

or NSDR protocol.

I've talked many times before on the Huberman Lab Podcast

about Non-Sleep Deep Rest, AKA, NSDR.

NSDR is sort of an umbrella term

for a variety of different practices,

so these are behavioral practices

that allow you to direct your brain and body

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and brain systems for teaching yourself

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it's also immensely beneficial just as a restorative

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Now, a number of people have reached out

about finding NSDR protocols, and there are a number

of different good ones out there floating around.

I've decided to put a zero-cost NSDR script

out there on the internet for people to access,

so you can find it by going to YouTube

and simply put my last name, 'Huberman' and 'NSDR'

into the search function.

This is a YouTube channel that's hosted by Virtusan,

which has a terrific app that includes NSDR

and a number of other health and wellness protocols,

but they've been quite generous

in hosting a 10 minute NSDR, read by me.

This NSDR is distinct from,

although I should say, similar to yoga nidra,

which some of you are familiar with.

This NSDR is different than yoga nidra

in the sense that it doesn't have intentions.

There's no mystical component,

and I describe a little bit of the science

and why specific components of the NSDR are included,

things like long exhale breathing,

I talk about perceptual shifts

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to pure sensation.

If none of that makes sense right now,

it'll make total sense after listening to the NSDR script.

Again, it's a 10 minute NSDR script, read by me.

You can do this first thing in the morning when you wake up,

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You could do it at any point during the day

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Again, this is a zero-cost resource for you.

You can find it by going to YouTube,

put my last name in and NSDR.

I encourage you to try it, and if you like it

or frankly, if you don't, you can just put that

in the comment section there on YouTube,

and I've put it there as a free resource to you,

so that you can benefit from the research-backed,

peer-reviewed studies that point to NSDR

as a very useful practice.

Before we begin, I'd like to emphasize that this podcast

is separate from my teaching and research roles at Stanford.

It is, however, part of my desire and effort

to bring zero-cost to consumer information

about science and science-related tools

to the general public.

In keeping with that theme,

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On many episodes of the Huberman Lab Podcast,

we talk about supplements.

While supplements aren't necessary for everybody,

many people derive tremendous benefit from them,

things like enhancing sleep and the depth of sleep,

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The Huberman Lab Podcast

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Let's talk about cannabis, and when we refer to cannabis,

we are indeed referring to marijuana or the marijuana plant.

Now, cannabis plants come in different strains

or different varieties, and those different strains

are indeed different genetic strains.

So just as animals and humans

have different genetic backgrounds,

and they can be crossed to one another

to yield further genetic variation in the offspring,

plants can be hybridized to one another

in various ways through grafting

or through the use of different types of seed combinations,

et cetera, in order to generate different strains.

There are also naturally occurring differences

in the strains of plants,

and the cannabis plant is no exception.

So for instance, in the context

of the discussion about cannabis

and its medicinal uses and recreational uses,

we need to distinguish between the sativa variety,

the indica variety, a variety called ruderalis

that's not often discussed,

and hybrids of sativa, indica and ruderalis.

Before diving into the different strains of cannabis

and how they impact the brain embody,

both similarly and differently,

I want to emphasize that the cannabis plant

contains a number of different psychoactive compounds.

Now, the most powerful of those compounds is THC.

The technical name for it is delta-9-tetrahydrocannabinol.

But THC, as I'll refer to it,

is just one of the psychoactive

and biologically active compounds within cannabis plants.

There's also CBD, which is technically referred to

as cannabidiol, and cannabidiol, CBD,

is known to be used for things like pain management,

anxiety management and other medicinal purposes.

We will talk about the efficacy of CBD for those purposes,

as well as some of, believe it or not,

some of the dangers of CBD,

depending on where it's sourced and the dosage, et cetera.

So we've got THC, CBD and also CBN or cannabinol.

CBN is less often discussed.

You're going to hear a lot less

about CBN containing products out there,

CBN containing medicines,

but it is relevant to today's discussion,

so it will come up a bit.

Now, I will be sure to provide more specificity

to what I'm about to say, but very broadly speaking,

THC is largely responsible

for the psychoactive effects of cannabis,

that is the changes in mood, the changes in bodily state

and sensation, et cetera.

Whereas CBD and to some extent,

CBN, have profound effects on the brain and body,

but they don't tend to give people the sensation

of altered perception, altered mood, et cetera.

Some people might say they are not the component of cannabis

that, quote unquote, gets you high,

although today, we will really drill into

what the high itself represents

in terms of chemical systems in the brain body.

And what we will soon learn is that

what we think of as being high actually includes

a number of different changes in the brain and body,

some of which can be best explained by CBD,

not by THC, which runs counter

to what most people out there know and believe.

So broadly speaking, we have THC, CBD and CBN.

But I want to point out that the cannabis plant

has over 70, seven-zero,

70 different psychoactive compounds,

many of which still have not been studied

in isolation and in detail.

So there's a big future of research for cannabis

and for THC and THC-related psychoactive compounds,

as well as for CBD and CBN.

Today we're mainly going to focus

on THC and CBD, as I mentioned before.

I should also point out that the cannabis plant

has over 400 biologically active compounds.

So these are biologically active compounds

that may or may not have psychoactive properties,

that may or may not be useful for pain relief, et cetera.

Again, there is a vast landscape for exploration

of the cannabis plant and of hemp for what they include

that could be beneficial to us or detrimental to us,

so again, a lot more work to do.

Today, we're going to really try and stay on target

with what we already know

and where there are certain exciting mysteries

or intriguing mysteries

about what we ought to explore more.

I will certainly highlight those.

Let's go back to the different strains

of the cannabis plant, sativa, indica and ruderalis

and explore how each of those

differentially impacts the brain and body,

because therein I think we can start to learn

a lot about this incredible plant

that is the cannabis plant.

And whether or not you are a user of cannabis

or whether or not you are entirely opposed to cannabis use,

understanding how cannabis works

in the brain and body, itself, is absolutely fascinating

and can teach you a lot about how your brain and body work

at a basic level and can tell you a lot about

how your brain and body will react to different life events

and how your mood is established and stabilized,

and how your appetite is established and stabilized

and so on.

So we have the three major strains of cannabis,

sativa, indica and ruderalis.

And for sake of today's conversation,

we can pretty much cross off ruderalis.

It's not often consumed,

and components of ruderalis are not often consumed

for medicinal or recreational purposes.

Let's focus on sativa and indica.

People will consume the sativa variety of cannabis

either by edible or by smoking cannabis,

or they will consume the indica variety of cannabis,

again by edible or by smoking cannabis,

or sometimes they will take it in a transdermal form

or a sublingual form.

There are a bunch of different ways

to get the cannabis into the body,

but there's a clear distinction between sativa and indica

that actually shows up first in the structure of the plant.

At their extremes, meaning in a pure strain of sativa,

it tends to be a taller plant, a longer stock,

believe it or not,

and actually the length of the leaves is quite a bit longer,

whereas the indica plant tends to be more short and stout.

And, for those aficionados out there,

I'm sure you know a lot of the other specific features

of sativa versus indica,

but already what we're talking about is the same plant,

cannabis, with two very different morphologies or shapes.

You might say, "Well, why is this interesting or important

"to how it affects me or affects other people

"for medicinal or recreational purposes?"

Well, it turns out that even though they are the same plant,

these two different genetic varieties,

because of the way that they grow

and the way they capture sunlight

and the way, believe it or not, that the different plants

within that strain interact with one another,

'cause believe it or not,

plants are interacting with one another,

they actually bring different elements

of the psychoactive compounds to different components

within the leaves and the so-called buds.

The takeaway is that when consumed,

and when I say consumed, I want to be very clear,

I don't necessarily just mean oral consumption

or eating cannabis sativa by edible,

I also mean smoking it, and that could be...

people will, just like with tobacco,

the way that they bring the psychoactive components

into their bloodstream and into their brain and body

is to essentially heat the dried leaves

of the cannabis plant.

Then the heat liberates some of the psychoactive components

that when inhaled into the lungs,

because the lungs include a lot of vasculature,

a lot of basically blood vessels and capillaries,

that the psychoactive components

are actually directly absorbed

from the lungs into the bloodstream,

and they can cross into the bloodstream

and permeate throughout the body

and cross the so-called blood brain barrier.

So in other words, burning the plant liberates the smoke

that contains the psychoactive compounds,

and those are inhaled into the lungs

and then get into the brain and body

and act on the brain and body.

And the major effect of sativa varieties

are to create a high, if you will,

and I'm putting this in air quotes

for those of you that are listening,

but to also act as a stimulant.

The sativa varieties tend to make people

feel invigorated, somewhat alert.

It doesn't tend to be as much of a sedative

as some of the other varieties.

Some people report heightened sense of focus

or heightened sense of creativity.

We'll talk a little bit later on

as to whether or not they actually

are achieving heightened levels of focus and creativity,

or whether or not they just perceive themselves

to have heightened levels of focus and creativity.

The sativa varieties tend to make people

feel a little bit less susceptible

to pain and noxious stimuli,

which are basically stimuli that you don't like.

So the sativa varieties are often prescribed or are used

in the recreational context for pain management and relief.

Basically, the sativa variety is known

to include a head biased effect.

So here, we're talking about subjective effects,

and of course these will vary

from one individual to the next.

Some people will smoke cannabis sativa

or ingest cannabis sativa orally

and will feel an entirely different array of effects,

but most people, the majority of people

experience a head-centered high, alertness, focus

and a sense that they're more creative.

Contrast that with the indica varieties of cannabis,

and when people smoke or eat or ingest indica varieties,

the psychoactive components of indica,

and again, this is pure indica,

so not hybridized with sativa at all, but just pure indica,

tend to lead to more full-bodied effects.

People report feeling more complete, full-body relaxation,

more of a sedative effect.

Indica cannabis is often prescribed

and/or used recreationally

in order to achieve a state of sleep

or to help relieve anxiety, so less of a stimulant effect.

And we will talk about why,

literally, the underlying neural circuits

that lead to the sativa variety causing more

of a elevated mood and a head high, if you will,

and the indica variety as being more full body relaxation.

One of the ways to remember the distinction

between the effects of cannabis sativa and cannabis indica

was relayed to me by a friend who actually was a chronic,

meaning every day, all day, consumer of marijuana.

He basically smoked marijuana for 20 years

before quitting about four or five years ago,

and he said that indica is often referred to

as 'in-da-couch,' meaning laid back in the couch.

And that can help you remember

that the indica varieties of cannabis

do tend to be more sedative in their effects.

Okay, so there's sativa and there's indica,

and then now there are hybrid strains.

So marijuana growers and people who specialize

in creating novel varieties of the cannabis plant,

again, I'm using the words cannabis and marijuana

more or less interchangeably here,

they are very good at creating new strains of plant

that might be 25% sativa and 75% indica or vice versa,

or 50/50 or 90/10.

Essentially, what's happening nowadays

is that through plant biology, plant genetics, I should say,

growers are getting quite efficient

at creating a variety of different strains

of the marijuana plant that give rise to very nuanced

and distinct effects on brain and body.

In fact, so much so, that there's now a new nomenclature,

a new language emerging around cannabis

and the development of novel strains of cannabis

for medicinal and/or recreational purposes.

And while this might sound a little bit medical

or a little bit clinical to some people, believe it or not,

this is the nomenclature that is now typically used.

People still refer to the sativa, indica and hybrid strains,

but there's now also a description

of so-called type one, type two and type three strains

for any given sativa, indica or hybrid strain.

Okay, so just to put this clearly in your mind,

you've got sativa varieties, that is pure sativa varieties.

You have indica varieties, again, pure indica,

and then you have hybrid varieties,

and beneath each of those,

you have type one, type two and type three strains

of indica, sativa or hybrid varieties.

What are type one, type two and type three?

Well, type one, type two and type three strains

are strains that have varying amounts

or ratios of THC to CBD.

So for instance, type one strain,

so for instance, you could have a pure sativa, type one,

or a type one pure sativa or a type one indica.

Those are going to have the greatest amount

of THC relative to CBD.

And I really want to emphasize this,

understanding the ratio of THC to CBD

can help explain a lot or even predict a lot

about how a given strain of cannabis will impact somebody.

For instance, because THC is largely responsible

for the typical psychoactive components of cannabis,

so what I mean here is, if somebody's ingesting sativa,

and it routinely makes them feel more energized,

elevates their mood,

it gives them a heightened sense of creativity,

if that's what they experience,

and they're taking a type one version of that,

that means that it's quite rich in THC and very little CBD.

However, if they were to take a type one version of sativa,

and it feels far too strong, like too much energy,

or they felt like they were too much in their head,

nowadays, there are strains of sativa

that have been genetically engineered,

and I don't mean by an engineer tinkering away

with gene engineering in a CRISPR creating mutes,

but literally by hybridizing,

crossing different plants to one another,

creating in a natural context,

the same way plants in the outside world

would sometimes hybridize to one another,

creating a variety that's perhaps type two,

which is going to have less THC and more CBD,

or a type three, which is going to be very high CBD

and very little THC,

and the same is also true for the indica varieties.

So I want to make sure that everyone understands this,

because it becomes very important

for understanding the biology of cannabis

and predicting positive versus negative effects of cannabis.

Sativa has this stimulant-like effect

and tends to be more of a head high, if you will.

Indica tends to be more full-body,

then lead to more in-da-couch, as I refer to it before,

pun intended, deep relaxation, reduce insomnia, et cetera.

Now, within each of those sativa and indica,

you have type one, type two and type three,

and that has everything to do with how much THC,

which is the dominant psychoactive compound,

versus CBD, which has other effects, mainly on the body,

but not so much on the brain

and modes of thinking and mood, et cetera,

how much THC versus CBD is present.

And again, type one is THC dominant,

type two, equal ratios, if you will, of THC and CBD,

and type three tend to be high CBD.

Okay, so already we've got some categorization here

that hopefully isn't overwhelming to you,

but this turns out to be extremely important

if you want to understand how cannabis works

and predict the effects of cannabis.

I'd like to take a quick break

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Okay, so somewhat surprisingly,

we're going to set aside cannabis.

We're going to take what we know about sativa, indica,

type one, type two, type three, CBD, et cetera,

and we're just going to set that aside for a moment.

Why would we do that?

Well, we have to ask ourselves,

why would any of these plants,

why would any of these compounds, THC, CBD,

sativa, indica, et cetera,

why would any of that have any effect on us at all?

And this discussion that we're about to have

very much resembles the discussion

that we had on a previous episode about nicotine,

because as many of you know,

nicotine is a commonly used substance.

In fact, if we were to look

at the three most commonly used drugs,

alcohol will be at the top of the list.

Many billions of people regularly use alcohol

or occasionally use alcohol.

Many billions of people also use nicotine.

It's the second most consumed drug, so more than 1 billion

and probably closer to 2 billion people consume nicotine,

and then the third most consumed drug

is cannabis in one form or another.

And many of you are probably shouting,

"What about caffeine? What about caffeine?"

Well, in the context of drugs,

and in particular, addictive drugs,

caffeine doesn't quite rise to the list,

but if we were to look at caffeine

and include it in that list,

caffeine would be above all of those.

But the most commonly used drugs are alcohol,

second after that is nicotine and then cannabis.

Nicotine, as some of you may know,

if you listen to the episode on nicotine,

but even if you didn't,

nicotine comes from the tobacco plant,

and there are a few other plants that include nicotine,

and typically it's brought into the brain and body

by smoking tobacco, dipping tobacco,

snuffing tobacco or vaping nicotine.

Nicotine exists in the outside world

in these plants, the tobacco plants,

but the reason it has an effect on the body

is that there are so-called nicotinic receptors in the body.

Now, those nicotinic receptors were named after nicotine,

the compound, but they existed in the brain and body,

not because of the existence of a tobacco plant,

but because there are other chemicals in the body

that naturally occur, namely acetylcholine

that bind the nicotine receptor.

Those chemicals, such as acetylcholine,

that bind the nicotinic receptor in your brain and body

create an enhanced sense of focus, et cetera, et cetera.

But, nicotine from tobacco binds that same receptor,

but with much greater affinity,

and therefore also creates a state of focus,

but a much greater one than we can achieve without nicotine.

So you can see the nicotine episode

if you want to learn more about that.

In a very similar way, all of our brains and bodies,

from the time that we are conceived, believe it or not,

very shortly after conception, if we want to be accurate,

very early conception, when you were in the womb,

and still now, if you're listening to this,

you have what are called cannabinoid receptors,

because you also have endogenous cannabinoids.

What do we mean by that?

You have receptors, which are like little parking spots

that are present on cells in your brain and body,

and what we call a ligand,

which is basically just a chemical that's released,

parks in that receptor

and causes a number of different biological effects.

Cannabis contains compounds

that also bind to those receptors,

but here I want to make a really clear distinction.

We have what are called endogenous ligands,

those just mean chemicals from within us

that we make naturally,

even if we never go near the cannabis plant

or any other source of cannabis,

we have chemicals that are created in us

that park in those receptors and cause biological effects

on mood, on perception, on the immune system,

on hunger, et cetera,

again, without ever going anywhere near cannabis,

we have these endogenous cannabinoids.

So endogenous cannabinoids are floating around in us,

or I should say, they are released in us

in particular ways, bind to these receptors

and cause changes in mood, appetite, et cetera.

They have many different effects on the brain and body,

and we'll talk about those.

But just like with nicotine,

there are substances in the outside world,

in this case, cannabis contains these substances,

so things like THC and like CBD, that when ingested

by smoking or vaping or by ingesting edibles

also will park in those same receptors,

the cannabinoid receptors and lead to biological effects.

Now, it's a little bit misleading,

because we call them cannabinoid receptors

as if they were there to bind cannabis,

or just like we call the nicotine receptors,

nicotinic receptors, it makes it seem as if they were there

in order to bind nicotine from tobacco,

but that's not the way our brains and bodies evolved.

Our brains and bodies evolved for these receptors

to make use of chemicals that exist within us,

called again, endogenous chemicals,

and those endogenous chemicals lead to certain effects,

as I mentioned before.

The key thing here,

if you haven't understood anything I've set up until now,

please understand this, the key thing is

that THC and CBD and the other components of cannabis

bind to those receptors,

those endogenous cannabinoid receptors,

the ones that we naturally make, with much greater affinity

and exert a vastly greater potency and effect

on mood and perception, et cetera,

than do our endogenous cannabinoids.

Another analogy that one could take

in order to understand this

would be hormones, like testosterone and estrogen.

Many people, I would say all people,

make testosterone and estrogen to varying degrees.

It's going to depend on whether or not you're male, female,

your age, whether or not you've gone through puberty,

et cetera, et cetera,

but let's just take testosterone for example.

There's testosterone circulating in your body.

That's true if you're male or female,

and there are receptors called androgen receptors,

we could even call them testosterone receptors.

And the testosterone binds to those receptors

and has effects on cells.

It causes hair growth, changes the voice.

It can affect libido.

It affects all sorts of things in the brain and body,

depending on which organ and tissue you're talking about.

But of course,

there are people that take synthetic testosterone

or derivatives of testosterone,

and some of those derivatives,

for instance, in the body building community

and the sports community,

they will take things like Dianabol.

These are modified versions of testosterone

that can bind to the testosterone receptor

with much greater affinity,

or I should say the androgen receptor

with much greater affinity,

and have supra physiological effects,

effects that would essentially never be seen

from testosterone that was endogenously,

excuse me, endogenously released within the body.

We could say the same thing for estrogen.

There are estrogen receptors, they bind estrogen,

but if someone were to take synthetic estrogen

or to ingest a plant compound

that contains various estrogenic compounds,

and those plants certainly exist out there,

they can have supra physiological effects

on those receptors.

Why am I telling you this?

Well, many people believe that because cannabis,

marijuana is a plant, and plants grow out of the ground,

and they're naturally occurring,

and because we have receptors in our body

that are there without the need to engineer them

from some external source, they're in our genome.

They're program for it, and we're born with these things,

and we keep these our entire life.

Many people mistakenly think, ah, these plant compounds

are safer for us or better for us,

or are somehow appropriate for us to ingest,

but that's simply not true, and here, I'm not saying

that cannabis is always a bad idea for people.

There are certain populations and certain people

for which it can be relatively safe recreationally,

that's the truth, and there are other populations

for which it can be downright dangerous,

recreationally or medicinally.

And of course, there are medicinal purposes

that are being explored, and we'll talk more about that.

But this is vital to understand,

because I think that when we hear,

"Oh, it's from a plant, it's natural,"

and then you also have a receptor for these,

endogenous cannabinoid receptors,

and therefore, the marriage of those two,

the coming together of the chemical THC or CBD or both

with these receptors is somehow supposed to happen

as if this was a purpose of having these receptors,

but it's simply not the case.

In the same way that the nicotinic receptors

are not there because nicotine is good for us,

they're there because there are compounds

that exist within us that are good

to bind to those receptors from time to time.

Now, here's the key thing about,

I guess today, I'm saying there are a lot of key things,

but here's another key thing about understanding cannabis

and the way that it works, which is that THC and CBD,

when they're brought into the brain and body

by smoking or edible, et cetera,

they bind to those receptors,

those endogenous cannabinoid receptors,

and they tap into the same systems

that your endogenous cannabinoids would tap into,

the ones that affect mood and energy

and creativity and relaxation, et cetera,

but they do so with thousand fold greater potency.

And as a consequence of that,

your endogenous cannabinoids are outcompeted.

They really get no opportunity

to interact with those receptors.

And understanding that,

can lead to a very clear understanding of why, for instance,

when people use cannabis to relieve anxiety,

or they use cannabis to enter a certain brain state

for creativity or to enter sleep,

why a dependence on cannabis starts to emerge.

Because if they don't ingest cannabis,

and again, ingest could mean smoke to bring THC in,

or CBD in, or ingest orally or even transdermal

or tincture or one of the other varieties,

if they don't do that, then what happens is

not only are the receptors not stimulated to the same degree

or with the same potency that they normally are,

but the endogenous cannabinoids

can no longer have their effect,

so people experience heightened levels of anxiety,

disrupted mood, disrupted brain state, and so on.

Now, again, I want to be very clear

that I'm not trying to paint a picture of cannabis

as all bad or even partially bad.

What I want to do today is give you

as much information I can as to how cannabis works,

how its different component parts work,

how the different types of cannabis work,

and point to some of the valid medicinal uses

and some of the recreational uses,

and then lay out the landscape for you

as to who is really most at risk

in terms of psychoactive components,

immune components and so on and so forth,

so that you can make the most informed choice for you.

I am not here to tell you what to do or what not to do.

As I like to say, do as you wish,

I mean, don't do as you wish

if it harms other people or yourself,

but do as you wish, but know what you're doing,

so that's really my goal here.

So as we begin to dive further into the biology,

I think you'll start to get a clearer picture

of why cannabis is so effective in some context,

but also why it can create such massive suffering

in other contexts because of the way

that it out-competes your own natural

endogenous cannabinoid systems.

So let's talk about those endogenous cannabinoid systems,

what they are and how they work,

because that will give us a lens

into what the higher potency or maximum impact

of the various cannabis plant varieties and strains

in THC and CBD and so forth, how and why those work.

So what are the endogenous cannabinoids,

these chemical substances that everybody makes?

You make them, I make them.

You've been making them basically

from the time that you were conceived,

and you are going to make them until the time that you die.

Whether or not they have the impact

and the biological functions that I'm about to describe

will depend a lot on whether or not

you are using your own endogenous cannabinoids

to park in those receptors that you also have

from birth until death,

or whether or not you are tickling those receptors

or strongly activating those receptors

using some external source like cannabis and THC, et cetera.

The two main endogenous cannabinoids

that we want to consider are anandamide,

which we will refer to as EAE, so anandamide,

and another one, which is arachidonoyl-glycerol,

arachidonoyl-glycerol, which we will abbreviate 2-AG.

So let's just take EAE and 2-AG, lump them together

and talk about the endogenous cannabinoids,

just to make it simple.

But if you want to do the deep dive on anadamide

versus 2-AG, please be my guest.

The endogenous cannabinoids are released from neurons.

What are neurons? Neurons are nerve cells.

And nerve cells should be conceptualized like this.

You have presynaptic neurons and postsynaptic neurons.

Presynaptic neurons basically contain little vesicles,

little bubbles full of neurotransmitter,

which are chemicals,

and when neurons are stimulated electrically,

and that could be from a thought,

it could be from the desire to move,

it could be because of a drug,

it could be because you're hungry,

the relevant neurons will vomit out or will fuse, as we say,

those little packets, those little bubbles

of neurotransmitter into the gap

between the pre and postsynaptic neuron,

and we call that a synaptic cleft or the synapse.

It's a little gap, a little space,

and the neurotransmitter flows across that synapse,

and some of it will park in the little parking spots

that we call receptors on the postsynaptic neuron side.

Depending on which neurotransmitter it is,

and a bunch of other things not worth going into right now,

the parking of that chemical

and those neurotransmitter receptors

will either cause that neuron on the postsynaptic side

to itself, release neurotransmitter elsewhere,

or it will quiet it down,

so-called excitation and inhibition.

That's kind of neuro transmission in a nutshell.

If you don't understand it, no big deal.

It's not going to prevent you

from understanding today's discussion.

If you understand even a small fraction

of what I've just said,

then it's going to allow you to understand

not just today's discussion, but a lot of neuroscience

with a lot more nuance and depth of understanding.

The key thing to know about the endogenous cannabinoids

is that unlike most neurotransmitters,

they are released from the postsynaptic side.

So what happens is neurotransmitter goes

from presynaptic neuron to postsynaptic neuron,

but under certain conditions,

the postsynaptic neuron, itself, releases a chemical,

and that chemical goes backward, what we call retrogradely,

to the presynaptic neuron, binds to receptors there

and changes the probability that the presynaptic neuron

will release neurotransmitter.

Put simply, endogenous cannabinoids

tend to decrease the probability

that a neuron will release neurotransmitter.

They're a break on the system.

They're a way of shutting down the communication

between neurons, regulating it,

not to make it completely quiet,

but to adjust the levels with a lot of nuance.

Now, the other thing that the endogenous cannabinoids do

is a mind bender, because we're talking about cannabis,

and a commonly known feature

of cannabis and marijuana consumption

is disruptions in short-term memory,

and there is essentially zero debate

as to whether or not that occurs,

and we'll talk about the mechanisms a little bit later.

And yet, endogenous cannabinoids,

the chemicals that you naturally release

from these postsynaptic neurons

that travel retrogradely back to the presynaptic neuron,

actually can lead to strengthening of connections

between the presynaptic neuron and the postsynaptic neuron

through a process called long-term potentiation, or LTP.

They can also cause

what's called depression of communication

between a presynaptic neuron and a postsynaptic neuron.

Long-term depression has nothing to do

with depression as a psychological state or as a illness.

Long-term potentiation and long-term depression

simply refer to the probability

that one neuron will be able

to stimulate and activate another neuron.

And, as I just told you,

the endogenous cannabinoids can either turn up the dial

or turn down the dial.

They can either increase the probability

or decrease the probability

that a given connection between neurons

will function more or will function less.

So if you think about the communication between neurons

as crosstalk, as a conversation,

well, the endogenous cannabinoids can dictate whether or not

that conversation is likely to occur or not to occur.

Think of them as either putting someone

at the top of your text chain in your phone,

which would be long-term potentiation,

or essentially blocking their number,

which would essentially be long-term depression.

So, if you're getting the impression

that the endogenous cannabinoids

are working in a number of different ways,

and it's not very straightforward, you're right.

In fact, that's the message that I'd like you to take away.

The endogenous cannabinoids

are sometimes increasing neuronal communication.

This can lead to increases in mood

or increases in the likelihood

that someone will talk a certain way

or behave a certain way or feel a certain way.

That can also lead to decreases in synaptic transmission,

that is communication between neurons,

in ways that will make somebody's mood lower,

or will make them less hungry or more hungry.

And, here's the really key thing,

there are two kinds of endogenous cannabinoid receptors,

referred to as CB1 and CB2,

and we can say with confidence that CB1

is highly enriched in the nervous system,

and especially within the brain.

It's found not everywhere,

but almost everywhere in the brain

and elsewhere in the nervous system,

so spinal cord and other aspects of the nervous system.

CB2, the cannabinoid receptor, CB2

is largely located in the tissues of the body,

including the immune system, the liver,

even the genitals, et cetera.

So what this means is that the endogenous cannabinoids

are having these sorts of effects

on neurons that I talked about,

but they are also having effects on immune cells,

on reproductive organs, on liver,

on digestion, on hunger, et cetera,

through mechanisms that are divorced

from the function of the nervous system of neurons.

Now, in reality, no system of the brain and body

is divorced from the nervous system,

because the nervous system is controlling everything.

It is really the master controller,

and everything's feeding back to the nervous system,

so it's a two way street.

But the simple way to think about it is CB1 receptors

are mainly in the nervous system,

and CB2 receptors are mainly in the body

and endogenous cannabinoids, again, EAE, anandamide,

and 2-AG, arachidonoyl-glycerol,

are impacting CB1 and CB2 receptors.

Today we're mainly going to talk about CB1 receptors,

'cause they are the ones that are responsible

for most of the familiar effects of cannabis,

but the key takeaway at this point is to really understand

that the major effects of your endogenous cannabinoids

on these receptors in this particular CB1 are very nuanced.

It depends on context, depends on which neurons.

It's sometimes increasing communication between neurons,

sometimes decreasing it, and then along comes cannabis,

and that cannabis, again,

can arrive by smoking, by vaping, by edible.

And cannabis contains THC and CBD

that potently bind the CB1 receptor,

and now the effects of the CB1 receptor

being occupied by THC or being occupied by CBD,

are not very nuanced.

In fact, they are very predictable

and especially important is to understand

that they are so strong, and they park in that receptor

with such affinity, with such force and precision

and stubbornness and refusal to leave that receptor

that they completely outcompete

the endogenous cannabinoid system.

In fact, they leave the endogenous cannabinoid system

essentially dysfunctional, which, in some cases,

may be a good thing, but in most cases,

is going to lead to problems of various kinds,

and we'll talk about what sorts of problems.

And again, I feel obligated to say,

this is not me saying don't ingest cannabis or THC or CBD.

That's not what I'm saying.

What I'm saying is if you evaluate the potency

that is in technical terms,

it would be the affinity with which these compounds,

THC and CBD and CBN, bind to these endogenous receptors,

that would be like a howitzer gun, like a cannon going off,

as compared to endogenous cannabinoid,

whether or not it's EAE or 2-AG,

which is more like a cap gun level of activation,

at least in this analogy.

So now you have what at least I would like to think

is a fairly complete understanding

of the different varieties of cannabis,

at least at a broad sweep,

and the different biological effects that they can have,

at least in terms of the major receptors

and in retrograde signaling, et cetera, et cetera.

Now, let's take a step back into the real world

and evaluate or think about

what happens when somebody smokes cannabis

or ingests cannabis by way of edible

or tincture or something of that sort.

Cannabis is very fast to enter the bloodstream.

In fact, within 30 seconds, it's going to enter the brain

and permeate throughout the brain and body.

That's very, very fast.

I mean, when you contrast that

with something like alcohol or even nicotine,

depending on how the nicotine is delivered,

that is a very fast delivery of the psychoactive

and biologically active compound,

which in this case is THC and CBD

and probably some other things as well.

So within 30 seconds,

it reaches the brain and bodily tissues,

and within 30 to 60 minutes,

it's going to reach its peak concentrations

and have its peak biological effects.

Those aren't always the same thing,

but in the case of cannabis,

again here I'm using cannabis as an umbrella term

for THC and CBD, the effects are going to peak

at about 30 to 60 minutes after bringing those compounds

into the body in some way or another.

And the effects tend to last

anywhere from three to four hours,

although there's some variation on that,

depending on individual metabolism,

whether or not somebody is familiar with the compound,

believe it or not, psychologically familiar,

but also biologically familiar,

or whether or not it's a first time use

or occasional use and so on.

THC and CBD and other components of cannabis

are highly what we call lipophilic.

That is, they have an affinity toward,

and they can actually pass through fatty tissues.

Now, every cell in your body, but especially neurons,

have a double layer of fat on their outside.

And of course, when people hear "fat,"

they always think, ooh, fat's bad.

Most of the world seems to want to lose fat or bodily fat.

Here we're talking about the fatty membrane,

the barrier around each tissue,

in this case we're talking particularly about neurons.

And THC and CBD and the other components of cannabis

are highly lipophilic, so they can get into

essentially all cells just simply by flowing into them.

They will also remain in those cells for a long time.

So, I know that a number of people,

depending on whether or not they get tested

for work or for sport or otherwise

for cannabis or CBD and THC,

don't take this as a strict number,

but typically, if one ingests CBD or THC,

smokes cannabis, ingests by orally, et cetera,

doesn't matter, it's going to stay in that fatty tissue

and can be detected for at least as long as 80 days

after ingestion, and there's a whole industry

as to how to accelerate the clearance,

and I should just tell you that just losing bodily fat

isn't going to eliminate it from your system,

maybe partially in those fat cells,

but certainly intravisceral fat and other fatty tissue

that's in around the brain and body

is going to harbor that THC molecule and the CBD molecule

for quite a long while, at least 80 days.

So, if someone smokes cannabis or they ingest cannabis,

it very rapidly gets into the bloodstream,

and the components that are psychoactive

get into the bloodstream

and are immediately able to access neurons and other cells

and start having these effects

of parking at those endogenous cannabinoid receptors

and impacting the signaling between neurons,

which leads to the subjective effects of cannabis,

including THC and CBDs, so let's talk about

what those different subjective effects are.

Again, this is going to vary depending on whether or not

people are ingesting sativa varieties of cannabis,

just to remind you, those tend to be elevated mood,

alertness, talkativeness.

People who take sativa varieties tend to talk a lot more

than they would otherwise.

Again, there are exceptions to this,

of course there are exceptions.

I'm sure there are people out there shouting,

although I guess if you're the quiet people

who don't talk too much, you're probably not shouting,

or if you're not, you're not doing on sativa,

Joe contended, but in any event, there are exceptions,

but there are also general rules.

And the sativas tend to make people's mood elevated,

energetic, again, this sort of head high,

and indica varieties tend to do the opposite.

more of a sedative, relaxant, et cetera.

Why and how would they do that?

Well, without going into an extensive deep dive

into the different neurotransmitter systems

of the brain and body, what we know for sure

is that CB1 receptors are present

on an enormous number of different neurons

in brain structures in neural circuits,

so that the sativa varieties that act as a stimulant,

making people feel happy,

'cause in general, they do tend to elevate mood,

at least at certain dosages, talkative,

tend to make people feel like they have ideas

that are interesting, that they might want to share,

tend to narrow their context, so we tend to increase focus.

This is something that's not often discussed about cannabis,

but especially the sativa varieties

can increase people's level of focus to particular things,

something they're watching or something they're doing

or music, it allows them to narrow their sense of focus.

That's going to occur by activation of CB1 receptors

in the so-called prefrontal cortex,

which is just behind the forehead,

and the prefrontal cortex acts as a strong modulator

of so-called limbic circuitry and other circuitry

that is more stress oriented.

The way to think about the stress and limbic circuitry,

such as the amygdala, which many people have heard about,

is that they aren't really circuits for fear and stress.

They are circuits that are constantly evaluating

one's own internal state, heart rate, et cetera,

and what's happening externally, and, sorry to say,

but the default of those systems is to detect danger,

so threat detection systems.

And then the prefrontal cortex largely acts

as a brake on those systems,

so like the reins pulling back on a steed of horses

that would otherwise just take off.

And so, the sativa varieties tend to increase CB1 activation

in the prefrontal cortex and in other circuitry

that then leads to an overall reduction in stress,

because of the way that prefrontal circuitry

can reduce activation or the amygdala.

Now that, of course, does not explain

why some people become very stressed and very paranoid

when they smoke sativa varieties

or other varieties of cannabis

or ingest other varieties of cannabis.

We'll talk about the paranoid effect and why that occurs

and who might predict that would occur to them

in a little bit.

But I just want to give you a sense of how this is working,

because as I mentioned before,

THC and/or CBD are going to bind that CB1 receptor,

let's say in prefrontal cortex,

the neurons of the prefrontal cortex, it's going to bind there,

and then they'll be a retrograde signaling

back to the presynaptic neuron,

and in the case of prefrontal cortex,

what's happening is it's increasing transmission,

increasing the release of neurotransmitter

in the prefrontal cortex.

However, at the same time,

the very same THC and CBD that was brought into the system

is binding the very same type of receptors, CB1 receptors,

in other brain structures, such as the amygdala

and causing retrograde signaling

back to the presynaptic neurons in the amygdala,

but it's quieting the activation of those neurons,

so this is interesting.

We have the same compounds, THC and/or CBD,

brought into the body and brain,

binding the same receptors, in this case the CB1 receptors,

but depending on where those receptors are located

and which brain areas we're referring to,

they are either causing heightened levels of alertness

and activation of systems that are designed

to make you talkative and alertness and mood, et cetera,

focus, or they're causing suppression of those circuitries.

So we have kind of a seesaw effect here

where the same compound is increasing mood and alertness

and focus in the prefrontal cortex

and is decreasing stress and threat detection

in the amygdala, and that's one of the reasons why,

especially the sativa varieties of cannabis,

allow people to enter these states of focus,

some might even say flow, although I don't want to go

into what flow states really are.

That's for a different discussion,

and it's very poorly defined as it is.

And I certainly don't want to give people the impression

that cannabis increases flow states,

because that's not always the case,

and certainly most often is not going to be the case.

But the idea here is that this molecule comes into our brain

and is shifting everything towards a state of focus,

elevated mood of heightened sense of importance

about whatever it is that we happen to be doing.

And now of course, whatever we could happen to be doing

could be writing a song, writing poetry,

communicating with somebody,

but it could also be something as trivial

as watching cartoons or watching a movie,

which is not trivial in its own right,

but in terms of thinking about the creative aspects

or the creativity stimulating aspects of cannabis,

not productivity oriented.

So narrowed focus, elevated mood,

more relaxed and yet energetic,

that's the major effects of the sativa varieties,

except, and this is a really big boldface,

triple underlined 'except,'

except in some individuals, depending on dosage,

but also depending on preexisting neural circuitry

and propensity for anxiety,

some people ingest or smoke sativa varieties,

and regardless of whether or not it's a type one,

type two or type three variety,

regardless of the ratio between THC and CBD,

people will experience intense anxiety and paranoia.

Now, how do you predict

who will experience intense anxiety and paranoia

and who will experience intense relaxation, focus

and sense of creativity from ingesting

or smoking a type one, type two or type three sativa?

Well, there is no way to predict that,

and there's a lot of what I would call street lore

or dorm room lore or not peer reviewed,

but peer discussed among friends and people

and acquaintances lore out there that what one needs to do

is simply smoke more, or just ingest more.

You hear that, "Oh, well listen, if it makes you paranoid,

"you simply need to use more,"

that is absolutely categorically false.

Everything we know about the way that THC and CBD work

is that they tend to potentiate,

that is increase the effects of these different systems

at given synapses and in different areas

of the brain and body.

That is, if someone experiences paranoia or anxiety

from a given strain of the marijuana plant

or from ingesting an edible in a particular way

or a particular kind of edible,

that person is very likely to experience the same effect

every time they ingest that strain or variety.

This is part of what's led to this enormous industry.

I mean, there are a number of different reasons,

but this is part of what's led to this enormous industry

of highly customized cannabis

where people will spend some time

really seeking out the different strains of cannabis

and hybrids of cannabis that work best for them

and work best for them in particular context.

I wish I could tell you that if you are a person

who is between 5' 7" and 6' tall,

and you have blue eyes or brown eyes,

that the sativa varieties are going to be right for you,

or that sativa varieties are going to give you panic attacks,

I can't do that.

The only way to determine it would be

to actually experience ingesting those or smoking those,

which is certainly also not what I'm suggesting.

That's up to you.

I'm not telling you what to do or what not to do,

but there are no good predictors.

In fact, if you look in the literature,

it is not at all clear that people

who have a heightened level of anxiety

when they do not smoke cannabis

will experience cannabis

as less paranoia inducing or more relaxing.

That's simply not the case.

Now, what we can say for sure

is that general categories of effects,

such as increased focus and reduced anxiety

are largely due to activation of areas

like the prefrontal cortex.

Now, unlike other compounds like nicotine or alcohol

or neurotransmitter systems like dopamine,

when we talk about the cannabinoid system,

and I say effects, biological effects, psychoactive effects,

I want you to keep in mind always,

please, please, please keep in mind

that those effects can be varied

and often opposite in direction,

so let's just give an example of that.

I just mentioned that when people smoke or or eat sativa,

that it tends to lead to one specific set,

or generally leads to one specific set of effects,

heightened focus, mood, et cetera.

Whereas when they ingest or smoke indica and its components,

again, we're still talking about THC and CBD

in varying ratios, but now indica cannabis, and you say,

"Well, why would it improve the transition time to sleep?"

Or at least give people the impression

that it improves the transition time to sleep.

We'll talk about what indica actually does

for sleep in a little bit,

but indica also tends to suppress activation

of the amygdala and threat detection centers in the brain,

again, binding the same CB1 receptors

in those retrograde signaling mechanisms

that I talked about before,

but it also tends to shut down the hippocampus,

an area of the brain associated with memory,

which is why indica varieties lead to pronounced,

or I should say profound defects in short-term memory

and sometimes in long-term memory as well,

if it's consumed over long periods of time.

We'll talk about short, medium and long-term consumption,

occasional consumption going forward.

So what I'd like you to take away

from this component of the discussion is first of all,

the mechanism of action

by which cannabis impacts the brain and body,

but in particular the brain,

is going to be through CB1 receptors,

and those CB1 receptors can lead to either an acceleration

or a brake on particular biological mechanisms.

And there are going to be a constellation

of different accelerations and braking

of different neural systems in the brain and body,

depending on whether or not people ingest sativa

or indica or some hybrid strain.

And perhaps most importantly,

even if you didn't understand anything

that I've said about the biology

of these different strains in the receptors,

please do understand that there is no way to predict

what the effect of a given strain will be on an individual.

There has been extensive exploration

as to whether or not people who are so called mellower

or more anxious or any number

of different personality dimensions

will respond in one way or the other,

but, in fact, there is no way to tell.

Layer on top of that the fact that dosing THC and CBD

can be fairly straightforward in the form of edibles,

because there can be, at least if it's a controlled source,

a defined number of milligrams of THC,

a defined number of milligrams of CBD.

That's true for ingestibles.

It's much harder to gauge that

from the smokeable forms of cannabis,

especially if those smokeable forms of cannabis

are obtained through sources

where there isn't a lot of clear information

about the total amount of THC in that product.

Now, this is all changing quite a lot nowadays

because of the commercialization of of THC and CBD products

and cannabis in a number of different areas,

including in the United States.

But still, many people are ingesting cannabis,

THC, CBD through sources where they don't really know

how much they're bringing into their system.

And so, whether or not someone

gets incredible anxiety relief, enhanced sense of mood

and focus and wellbeing, pain relief, et cetera,

or whether or not they have full blown panic attacks,

et cetera, is very hard to predict

based on dosage information alone.

Now, of course, we can create broad categories,

and we are going to talk about studies

that create broad categories of low dose, moderate dose,

and high dose. frequent use and infrequent use,

but unlike alcohol, unlike nicotine,

we can't really point to specificity of X amount of alcohol,

grams of alcohol per week, which is safe,

or X amount of alcohol, which is not safe.

And so I know a lot of people out there are wondering,

how often can they smoke cannabis,

or how often can they eat cannabis or THC or CBD

in any number of its different forms and products, safely?

Well, we have to really define what 'safely' means,

and we have to really acknowledge

that there's a pretty loose set of controls

over what one is bringing into their brain and body

as they ingest THC and CBD,

but even under conditions in which it's very controlled,

it's very hard to predict what those effects will be.

So before moving into specifics

of taking cannabis or not taking cannabis,

who should, who shouldn't,

what the medicinal purposes are

and what some of the newer, exciting data point to,

I just briefly want to make a list,

and I promise very briefly, I know I'm not often concise,

but I do try to be thorough for your sake.

I want to make a very brief list of the different brain areas

that are impacted by THC and CBD

and why THC and CBD have the various effects they do.

When somebody smokes or ingests cannabis,

doesn't matter what the THC or CBD ratio is,

if they experience deficits in memory,

and that's almost always present, that's going to be

because of reductions in electrical activity

within this brain region we call the hippocampus.

Hippocampus means seahorse. It's shaped like a seahorse.

Anatomists like to name things after what things look like,

but hippocampus memory, memory is reduced,

in particular short-term memory.

That's true regardless of whether or not

one is using sativa indica or some hybrid.

In general, the prefrontal cortex is going to be activated

by the sativa varieties, which is going to increase thinking

and narrowly constrain focus to some activity,

and that's more commonly associated

with the sativa varieties.

The indica varieties, as I mentioned before,

tend to lead to a suppression of activity

in prefrontal cortex, believe it or not,

and turn off thinking and planning.

This is why indica varieties are often used

for relaxation and for promoting sleep.

Regardless of whether or not sativa or indica variety,

and again, regardless of the ratio of THC to CBD,

there is a general suppression of neural circuits

within the so-called basal ganglia and cerebellum.

Basal ganglia and cerebellum are areas of the brain

that are involved in action planning and withholding action,

so that would be the basal ganglia,

so-called go, no go circuitry,

and the cerebellum, which is involved in balance,

but also motor planning and motor sequencing.

This is why people who smoke marijuana,

regardless of the strain,

will tend to be less physically mobile.

Other common effects are reddening of the eyes,

dryness of the mouth,

that's actually caused by the same general mechanism,

which is a reduction in the secretion of saliva

and of tears and lubrication of the eyes

from the lacrimal glands of the eyes

because of the presence of largely CB2,

but also CB1 receptors in the mouth and on the eyes.

And there tends to be,

especially with certain strains of cannabis,

increase in appetite, so-called munchies,

and that has everything to do with very, very high density

of CB1 receptors in the hypothalamus,

and in particular areas of the hypothalamus,

like the arcuate nucleus of the hypothalamus,

other areas as well, of course,

that have tons of CB1 receptors, bind THC and CBD

and activate the neurons that strongly stimulate appetite

through two mechanisms, one is a cognitive mechanism

of creating a preoccupation with food

in anticipation of taste,

as well as the experience of taste.

So the narrowing of focus to what you want to go eat.

You really crave, I dunno, pizza.

It seems to be high fat, high carbohydrate foods,

but really crave pizza and narrowing of focus,

so that you're not thinking about anything else,

but also signaling from the hypothalamus to the gut

to neurons within the stomach, itself,

that regulate blood sugar,

so there are strong effects on blood sugar of THC and CBD

that generally lead to increases in appetite,

so two parallel mechanisms, one within the brain,

one within the body, increasing appetite,

so there's an array of different effects.

And as I mentioned before, CB1 receptors are present

all over the nervous system in the brain, the spinal cord.

In fact, the presence of CB1 receptors in the spinal cord

largely explains the fact that THC and CBD, to some extent,

although it's not very well studied,

can provide some pain relief.

I say some, because a lot of people perceive

or believe that they experience more pain relief

from cannabis than they actually do.

It actually has a lot to do with a perceptual shift

to basically focusing on other things,

but there does seem to be some antinociceptive,

meaning anti pain effects of cannabis, THC in particular,

and that is exerted largely through effects on CB1 receptors

in neurons of the spinal cord.

So a broad array of effects are taking place,

regardless of what strain you take

and whether or not you eat the cannabis

or you smoke the cannabis.

And the broad array of effects can be explained by the fact

that that retrograde signaling can lead to activation

or suppression of activity in various neurons.

So now I'd like to take a step back

from the biology of cannabis and THC and CBD

and all the signaling and receptors, et cetera,

and really just focus on cannabis use,

and wherever possible,

I will point to the specific strains that have been studied

and the ratios of THC to CBD,

but I have to say that unfortunately,

most studies of marijuana, of cannabis,

while they have been very careful

to detail the amount of THC,

low dose, medium dose, or high dose,

and actually getting very specific,

right down to the number of milligrams

or even how much circulating THC is present

after somebody smokes a joint or ingests cannabis,

most studies have not distinguished

between sativa and indica strains.

And that's unfortunate, because in the real world,

people are distinguishing between sativa and indica strains

in their patterns of use and what they prefer

and what they don't prefer,

or even what they prefer to smoke during the day

or ingest during the day versus night.

Believe it or not, there are people

who are using certain strains during the day

and other strains at night,

but the science is yet to catch up to that,

or I should say, more accurately,

the general public and the themes that are emerging

and the practices that are emerging around cannabis,

especially in states where it's decriminalized or legalized,

are occurring at such a rapid rate

that there's absolutely no way

that the science could keep up.

This is a naturally occurring experiment,

not to say that it's natural, like people should do it,

but it's an experiment that's happening in real time

in the real world, much faster than controlled studies

within university laboratories

and other laboratories can keep up.

So at this point, I think it's appropriate to ask ourselves,

why do people even use cannabis?

What are they trying to achieve?

Is it always about not feeling pain?

Is it always about reducing anxiety?

Well, sometimes it is,

but oftentimes people are using cannabis

in order to achieve a particular state.

And we could use a broad brush and say,

"Well, they just like being high,"

but while that may be true in a lot of circumstances,

and I have to believe it actually is true

in a lot of circumstances,

there are a lot of people who use cannabis

in a very directed way, or they get, quote unquote, high,

in order to achieve states

that to them are particularly attractive,

and one such state is a state of creativity.

And this brings us to a broader theme,

which is, does cannabis increase creativity?

And if so, is it the THC, the CBD,

what's the appropriate ratio

or the best ratio for accessing creativity?

This is an interesting and important discussion, I believe,

because creativity is one of the more sought after

and more elusive states that humans can experience.

And yet, if you look at human evolution,

you look at our progression

in terms of technology development

and culture and music and poetry, et cetera,

we really can look to creativity as the state

that fostered so much of that evolution.

So whether or not you're into technology,

or you're into art or music,

whether or not you're just somebody

who wants to expand their understanding

or their experience of life in some way,

creativity is a fundamentally important state

to try and access and to try and access regularly

and to try and tap into,

in order to eventually produce something,

in order to create something of meaning

that exists not just in that creative state,

but to yourself after that creative state has gone away,

so the painting that you paint in the creative state

hopefully is a painting that still inspires

and has impact after you exit that creative state

and that will inspire others, and this could be true

for any number of different things, not just painting.

So does cannabis increase creativity?

The short answer is, it depends.

First of all, we need to define creativity.

Here we are, thinking as scientists,

if not already scientists,

and there are basically two modes of thinking

that are associated with creativity,

and they don't completely explain creativity.

But if you look in the research,

the psychology research and the neuroscience research,

you'll hear about convergent thinking

and divergent thinking.

Convergent thinking is taking loose ideas

and kind of braiding them together,

finding a common thread, synthesizing,

and organizing those different ideas

into some common or specific framework

in order to get or create some specific outcome.

So convergent thinking is basically the person in the room

who's listening to all the ideas and taking them all in.

Maybe it's a panel of, how should we

get a certain product out to market?

Or what are the different motifs

that we should include in a piece of music?

Or what should we do

in terms of rearchitecting a given physical space?

Taking in those different opinions,

those different ideas from different people,

and then synthesizing them and coming up

with one or a small subset of coherent ideas

that incorporate some or all of the ones that they heard,

so that's convergent thinking.

It doesn't have to involve a panel of people talking to you.

I use that as an example

of what goes on inside your own head

when you are engaging in convergent thinking.

You're thinking, well, so and so said this,

and I think that, and you're braiding them through

and trying to get some common themes,

some common vector to emerge from that.

Divergent thinking, on the other hand,

is best described as brainstorming.

It's exploring ideas and continuing to move

into the variation and the vastness of ideas

in hopes of eventually being able to converge

on some novel idea or framework.

So these are similar and related,

but typically the creativity process

involves first brainstorming and divergent thinking,

and then in order to arrive at something,

to actually create something, the verb 'create,'

not just thinking about what you might create,

which occurs during divergent thinking,

but actually creating something, a specific painting,

a specific song, a specific body of literature,

a specific scientific project or experiment and so on,

that usually involves convergent thinking.

Now these can be explored in the laboratory,

and they can be explored in the laboratories

through sets of different types of questionnaires

or even tasks that you can give human subjects,

and this has been done extensively

and across the entire body of data,

and by that I mean, literally hundreds of studies

that have explored the relationship

between particular neuro circuits and neurochemicals,

convergent and divergent thinking.

We can arrive at a principle,

and the principle involves a molecule

that many of you have heard about before, which is dopamine.

Dopamine is a neuromodulator.

It's involved in motivation,

and it tends to direct our attention

to things outside of us, but it's also closely related

to convergent thinking and divergent thinking

and to the creative process.

And therefore, it should come as no surprise

that diseases of the nervous system, excuse me,

such as bipolar disorder,

which we've done in episode all about bipolar disorder

or schizophrenia or mood disorders

that impact the levels of dopamine,

either make it way, way too high or way, way too low,

strongly impact whether or not people will be creative.

And I think the short takeaway that makes the most sense

in terms of framing this,

and we covered this on the episode on bipolar disorder,

sometimes called bipolar depression, is that in professions

where there's a lot of creativity required

in order to succeed, so again, musicians, composers,

artists, et cetera, you tend to find more manic depression,

and manic depression,

at least in the manic states, the hyperactive states,

are correlated with elevated levels of dopamine.

Likewise, it has been seen over and over throughout history

that individuals that have mild forms of schizophrenia,

or even full-blown schizophrenia,

many famous painters for instance, or musicians,

they are known to have elevated levels of dopamine,

and they are quite creative.

Now, that doesn't mean everybody who's creative

has elevated levels of dopamine,

although it's likely that their levels of dopamine

are at least not diminished,

and it doesn't mean that non-creative people

have low levels of dopamine,

so don't get carried away with the interpretation here.

But the point is this,

dopamine levels strongly relate to the probability

that you can engage in convergent and divergent thinking,

and they do so in the following way.

When dopamine levels are high,

divergent thinking is more likely.

That is, when people have a lot of dopamine

circulating in their system,

they tend to be very expansive with their ideas,

they tend to brainstorm a lot,

they tend to be comfortable and even want to,

or reflexively throw out a lot of ideas

so that sometimes even seem a little disconnected.

Some people might think of this

as attention deficit, but it's not.

It's really the idea of throwing out disparate ideas.

You hear sometimes, you throw things against the wall

and see what sticks, that's a obviously an analogy,

but people are throwing lots of things against the wall

and seeing what stick,

and then seeing how the things that stick fit together,

that's divergent thinking, and elevations in dopamine

tend to increase divergent thinking.

However, they tend to do this in an inverted U-shape way.

For those of you either watching on YouTube,

I'm just drawing a hump, obviously,

and for those of you listening,

just imagine a U, the shape of a letter U,

and then just flip it upside down, so it looks like a bump.

Turns out that when dopamine levels are very low,

there's a low probability of divergent thinking.

When dopamine levels are high, as I mentioned before,

there's a high level or probability of divergent thinking.

But when dopamine levels go very, very high,

then there's again, a reduction in divergent thinking.

In other words, there's a sweet spot

of elevated dopamine for divergent thinking.

And again, divergent thinking

is critical for the creativity process,

because creativity by definition

is taking a novel set of ideas

and arranging them in a particular way,

or taking existing ideas and arranging them in a novel way

that then you eventually converge

on some new product, new idea, new song, et cetera.

Now, convergent thinking follows a very different pattern.

When dopamine levels are high,

convergent thinking is not very likely.

And when dopamine levels are low,

convergent thinking is very likely.

So here, using arguably a very reductionist view,

we're looking at all of this thing we're calling creativity

through a very neurosciencey reductionist lens,

we can say this.

The creative process involves going into a state

where you're willing to consider a lot of options,

many of which seem distantly

or not even connected to one another,

and dopamine facilitates that divergent thinking state

in which you are perfectly happy

and in fact, experience a joy, or elation, a comfort

and a pleasure in organizing all these different ideas

that to anyone else might seem not that related.

But when your dopamine levels are elevated,

these all seem like great ideas

and that maybe there are connections there.

You're not accepting all of them as true and valid

and interesting in combining them, but there's this idea

that it's worth entertaining the possibility,

at least for moments.

And then, as dopamine levels drop,

there is the process of convergent thinking,

which is taking options down off the wall saying,

"No, no, that doesn't fit with that,

"that doesn't fit with that,

"but ah, that fits with that, and that can work.

"That feels right or sounds right or looks right."

That's the creativity process.

And so, I think this is not just important

for understanding cannabis,

which we'll get back to in a moment,

but it's important for understanding creativity

and brain states in general.

Brain states are not, as we would say,

a square wave function.

You don't just drop into a trench of creativity.

Creativity is not an event, it's a process.

And what I'm telling you is that it's a process

that involves divergent thinking

and consideration of a lot of different ideas.

That's correlated with high but not too high dopamine.

And then, one has to transition into a state

of convergent thinking, which is really honing in

on the ideas that seem to have validity

or that could have validity

and getting rid of everything else,

and that's associated with low dopamine.

It's more about logical implementation and consideration

as opposed to thinking about and considering everything.

So let's now return to the question

of whether or not cannabis

and its different components increase creativity.

And when you look at the literature on this,

you find studies that very clearly point to a yes,

it increases creativity, and it's not surprising,

therefore, that cannabis can increase dopamine transmission,

that is dopamine levels, in certain brain areas,

in particular brain areas involved in thinking and planning.

So cannabis increases dopamine in these areas.

Elevated dopamine increases divergent thinking,

and divergent thinking is associated with creativity,

and there are studies that support the idea

that cannabis can increase creativity.

However, there are at least as many studies

that say that cannabis does not increase creativity,

that cannabis increases consideration of multiple ideas,

perhaps through elevation of dopamine and related systems,

but that ultimately the ideas that converge from that

are not truly creative ideas,

at least they don't meet the criteria

for creative brainstorming

and extraction of ideas that are truly novel,

so it doesn't increase creativity, so which one is it?

Well, fortunately,

there's an entirely distinct set of literature

that has taken all the other literature into consideration,

and here's where we arrive.

So there's a really nice study

that explored creativity in cannabis users,

and we will provide a link to this study.

First author is Emily LaFrance,

and the title of the paper,

somewhat amusing in its own right,

which is, it starts with a question,

inspired by Mary Jane, of course,

Mary Jane being one of the old school versions

or ways of talking about cannabis or marijuana.

Nowadays, people refer to it mainly as pot,

as other names too, of course,

and the title of the paper is,

"Inspired by Mary Jane Mechanisms Underlying

"Enhanced Creativity in Cannabis Users."

And I really like this study for a couple of reasons.

First of all, they looked at people who did not use cannabis

as well as people who used cannabis,

so they had two different groups,

but they did not evaluate creativity of the cannabis users

while they were under the influence of cannabis.

They looked at the level of creativity

in these cannabis users

when they were not under the influence of cannabis

and asked whether or not their ability to be creative

was enhanced by cannabis.

Now we're going to compare this to studies

in which people come into the laboratory

and actually use cannabis,

and then they evaluate creativity under that context.

But this study has some unique takeaways

that I think are really interesting.

First of all, they did, yes,

see evidence for enhanced creativity,

and when I say enhanced creativity,

I mean within the context of this divergent thinking thing

that I talked about a moment ago.

And when I say enhanced,

I mean significantly greater than in non-users,

so people that don't use cannabis.

So right now I can imagine that all the cannabis users

are cheering, "Yes, cannabis increases creativity,

"makes people more creative than they would be otherwise."

Well, this is interesting.

We have to ask ourselves how that was accomplished.

And it turns out that one of the major ways

in which it was accomplished is that cannabis users,

even if they're not under the influence of cannabis,

are far more open to novel ideas,

and they have a more explorative and reduced anxiety,

or I should say lower anxiety mode of thinking

when they explore novel ideas,

which is essential for divergent thinking.

So they observed both enhanced divergent

and convergent creative type thinking in cannabis users.

And the source of that, they conclude is,

and here, I'll just quote, "Cannabis users' higher levels

"of openness to experience are responsible

"for their enhanced self-reported creativity

"and convergent thinking test performance."

So it's not necessarily that cannabis

is increasing the capacity of the brain areas

that are associated with creativity,

but rather, cannabis appears to be increasing an openness

and probably doing that in part through lowering anxiety

in particular people, and that openness

is leading to inclusion of more ideas

during the divergent thinking process.

They're willing to consider throwing up

more things on the wall to see if they stick, so to speak.

So in their conclusions, they have a really nice statement.

Again, I'll just read from the paper,

because they said it better than I ever could, quote,

"While mainstream media has propagated the idea

"that cannabis expands the mind and enhances creativity,

"our results show the link between cannabis and creativity

"is largely a spurious correlation,"

meaning that it's not the case

that cannabis increases creativity, but,

and I inserted the 'but' in this quote,

but "driven by differences in personality

"that are related to cannabis use.

"For example, openness to experience that are related

"to both cannabis use and augmented creativity."

This is a real chicken/egg argument. What do I mean by that?

What I mean is, this paper finds

that people who are more open to experience

are more likely to use cannabis,

and people who use cannabis

are going to be more open to new experiences,

and that combination of features, openness to experience,

and what that openness to new experiences brings,

enhances the convergent and divergent thinking

that is characteristic of the creative process.

So in short, cannabis increases creativity,

but through changes in personality

that tap into the creative process,

rather than directly impacting the neural circuits

that, for instance, turn on creativity.

And I have to say, this study is really important,

because by exploring cannabis users,

not while under the influence of cannabis,

they were able to tap into this very important,

what I believe to be fact.

Because if you think about a study

in which you would have one group using cannabis

and another group not using cannabis,

and then you give them some task that taps into creativity,

you will see effects and very likely,

you'll see effects where cannabis might even increase

divergent and convergent thinking and creativity.

Those results have actually been published

many times before.

But given the varied effects of cannabis and THC

that we talked about earlier,

through all of that complex signaling stuff,

you can imagine that there will also be other studies,

and in fact, there are,

where divergent and convergent thinking and creativity

is not assisted by cannabis

and might even be reduced by ingesting cannabis.

However, if one considers that divergent thinking

is absolutely crucial to the creativity process

and the range of things that one will explore

will be enhanced by openness

and by reduced levels of anxiety,

so a willingness to explore different options,

some of which might seem completely crazy,

and cannabis increases the personality types

and reduces the anxiety that create that sense of openness,

well then it makes perfect sense

why cannabis would increase creativity

in certain individuals, but not directly.

And this study, the one I just referred to,

which I should say was published

in the journal, "Consciousness and Cognition,"

and again, we'll provide a link to it,

did a wonderful job of teasing out

this impact of cannabis on personality,

which then impacts creativity.

So if somebody asks you, or if you're wondering,

or if you feel like cannabis increases creativity,

in some sense the answer is 'yes,'

but the answer is 'yes' because of the ways

that it shapes openness to new ideas

and can, I should say 'can,' because not in everybody,

but can, in some individuals, reduce anxiety.

What this means is that if you are somebody

who experiences anxiety or increased levels of focus

from cannabis, regardless of the strain,

and here I have to imagine people

are exploring different strains,

if they're exploring them at all,

exploring different modes of delivery,

smoking or ingestible, et cetera.

If you're somebody who experiences anxiety,

it's very likely that you won't have the increased openness

to experience and divergent ideas

that will facilitate creativity.

However, if you are somebody who achieves heightened levels

of relaxation and reduced levels of anxiety from cannabis,

regardless of which strain we happen to be talking about,

well then, yes, it will position you

to be in a heightened state of creativity,

at least as defined by convergent and divergent thinking.

One of the more characteristic,

or I should say stereotype qualities of people

that smoke a lot of marijuana or ingest cannabis

through other means is there changed patterns of speech.

In fact, there's a lore in the clinical realm

that you can predict or get some strong indication

as to whether or not somebody is a cannabis user

or pot smoker based on their voice

and their particular tone of voice

and their lack of inflection.

There's a lot of speculation here,

but fortunately, it's been studied.

So I'd like to discuss now

whether or not cannabis can impact patterns of speech,

both acutely, meaning while under the influence of cannabis,

and over time, in chronic cannabis users.

And when I say 'chronic cannabis use,'

I want to be very specific what I mean.

Chronic cannabis use does not necessarily mean

that people are smoking cannabis

or ingesting cannabis every day,

although certainly if they are,

that qualifies as chronic use.

Chronic use is regular use over time

of anywhere from twice a week or more.

So using cannabis once a month

would not be considered chronic use,

even if it's for many, many years.

Using cannabis or ingesting cannabis

in some way or form twice a week

would be considered chronic use.

Then of course, some of you out there

are going to ask me to split hairs and say,

"Well, what if somebody uses it twice a month?"

Well, listen, the clinical literature,

and the scientific literature don't get that specific.

And of course, they're an infinite number of ways

to arrange one's cannabis use,

everything from zero, none at all,

to constantly, every day, all day and everywhere in between.

But think of chronic use as twice a week or more.

Think of occasional use as less than that

and realize that within the realm of chronic use, excuse me,

that 'or more' can be anywhere from twice a week,

to every day, to just in the evenings, et cetera.

The effects of chronic use of cannabis,

as I just defined it, on speech have been studied.

Because of this characteristic,

drawing out of certain syllables, a slowing of speech,

and in many cases a total change or alteration

in the way that people speak and use language,

both when under the influence of cannabis

and when not under the influence of cannabis

if they're chronic users.

And here we really want to distinguish between THC and CBD

and just make it really simple and say

that CBD is not responsible

for most of the psychoactive effects of cannabis,

whereas THC is, and again,

the ratio of CBD to THC is going to be relevant there,

but let's just think about cannabis and THC

as one in the same for this portion of the discussion,

realizing that, of course,

they are not exactly the same thing.

There's an excellent study entitled,

"Adults with History of Recreational Cannabis Use

"Have Altered Speech Production,"

and we will provide a link to that,

first author, Adam Vogel, really like this paper.

It was published in the journal,

"Drug and Alcohol Dependence."

We will provide a link to it for you

if you'd like to peruse it in more detail.

The title itself, "Adults with a History of Recreational

"Cannabis Use Have Altered Speech Production,"

tells you pretty much everything you need to know,

except there's some important nuance in here,

because, as I mentioned earlier,

people who smoke sativa varieties of cannabis

oftentimes will become more talkative, much more talkative.

However, whether or not people tend to rely

on sativa cannabis use or indica cannabis use,

there is a very consistent finding

that people who are chronic users,

again twice a week or more,

recreational use or medicinal use,

undergo pretty profound changes in the way that they speak,

but in a very specific set of ways.

Now, first of all, the changes in speech

shouldn't surprise us at all,

because both sativa varieties of cannabis

and indica varieties of cannabis

impact those brain centers involved in movement,

the basal ganglia, remember the go, no-go circuitry,

the circuitry that makes you want to do things,

and the circuitry that makes you want to withhold action?

And it tends to shift the body and brain

toward more inaction.

And cannabis impacts CB1 receptors in the cerebellum,

which is involved in motor planning, execution and balance.

So, regardless of whether or not people

are using cannabis of the sativa or the indica variety,

there are disruptions in motor circuitry.

And, as you may have heard,

if you listened to our episode

with Rockefeller professor, Dr. Erich Jarvis,

who works on speech and movement, speech is movement.

The movements of the mouth, the movements of the hands,

those are intimately related in terms of our speech.

In fact, the centers of the brain involved in hand movements

are part of the speech areas and vice versa.

Erich actually pointed out

that if you put your hands behind your back,

provided you normally do have use of your hands,

it actually will reduce your fluidity of speech,

and so I'm going to put them back in front of me now.

The point is, smoking marijuana or consuming marijuana

by edible changes one's speech

and does it in a very specific way.

And in this study by Adam Vogel and colleagues,

they explored a huge different variety of aspects of speech.

And this can be done using spectral processing,

which is fancy nerd speak

for looking at how much inflection there is

or looking at how long people hold vowels

or consonants, et cetera, and again,

these are people not under the influence of cannabis,

but rather people who tend to be under the influence

of cannabis when not participating in the study,

in other words, chronic recreational cannabis users.

So what are the two major shifts that cannabis causes

on our patterns of speech?

Well, the first one is a change

in what's called spectral tilt.

Again, that's fancy nerd speak

for vocal effort and intensity.

So, I'm not a pot smoker, I confess,

but if I were to say the sentence,

"Vocal effort and intensity

"are important components of speech,"

that's the way I would say that sentence

if I was striving to enunciate very carefully

and to accent certain words and syllables.

A pot smoker or somebody who uses recreational cannabis

fairly often would have reduced spectral tilt,

AKA, vocal effort intensity, and might say,

[mumbling] "Spectral tilt is vocal effort in intensity,

"and it differed between groups and appeared to change

"in line with the duration of abstinence from cannabis use."

That I think is not a far cry

from the change in spectral tilt that they observed here.

In addition, there are changes in verbal timing,

that is pronunciation of words

and accenting particular syllables of words

in people that consume cannabis or smoke cannabis.

So rather than emphasize particular words within a sentence,

so again, I'll just use a sentence from the paper

so that you can gain more knowledge from the paper,

"Cannabis," and I'll say it the way that I would say it,

since I'm not a cannabis user.

"Cannabis, marijuana, is the most commonly used,

"illicit drug in the world with approximately 4% of adults,

"aged 15 to 64 years reporting recent use,

"and the citation is from the United Nations Office

"on Drugs and Crime, 2019."

So that would be the way

that I would typically read that sentence.

And having gone into the data on this paper,

and of course evaluated references therein

and listened to some of the spectral analysis

that they include as data,

you can literally go into these papers online

and hear recordings of people who are cannabis users

or non-cannabis users,

and I'll try and give you a a clear sense

without picking an extreme example of how somebody

who's a fairly consistent or even occasional cannabis user

might read that very same sentence.

"Cannabis, marijuana, is the most commonly used

"illicit drug in the world with approximately 4% of adults

"age 15 to 64 years reporting recent use,

"and the citation comes from the United Nation Office

"on Drugs and Crime in 2019."

Now you'll notice that wasn't a dramatic difference.

And, of course I could have taken the liberty

to pick an extreme example of the sort

that they did occasionally observe

in evaluating subjects for this paper.

I could have said something like,

[mumbling in low tone] "Cannabis, marijuana,

"is the most commonly used illicit drug,"

but frankly that would've been selecting an outlier example,

and I don't want to do that.

I don't want to skew the data as they say.

Rather, if you heard the first time I read the sentence

and the second time I read the sentence,

what's mainly different is the difference

in the amount of enunciation and accenting

of particular words and symbols within a sentence.

So the total content that's delivered is exactly the same,

and while I wasn't measuring my pace,

the overall rate of communication is essentially the same,

but there's less lilting and falling of the voice

and less accenting.

That's the major consistent effect of cannabis use.

Now of course, there are examples of people

who are using a lot of cannabis,

and it impacts brain centers

involved in movement and speech,

so much so that they really do have

the really drawn out kind of, nah,

and oftentimes this will be detected in the laugh.

There's this stereotypical stoner laugh,

as it's sometimes called.

Rather than say "Ha, ha, ha"

or that's a fake laugh, obviously.

It's hard to make myself laugh

if something's not actually funny.

I'll have to think of something funny.

When people say like, "Ha!"

That's a bit more of the way I might laugh,

like, "Ha," sort of the inspiratory laugh

or the, "Ha," which is expiratory laugh.

People who use cannabis chronically

will often do that, "Haa," which is the back of the throat,

[laughs raspingly] it's neither inspiratory

nor expiratory laugh, and believe it or not,

there's an entire literature

on inspiratory, inhaling, versus expiratory laughs,

and there's also a literature on cannabis

altering the pattern of inspiratory and expiratory laughs.

It almost sounds like a sarcastic laugh

when, in fact, they may not be feeling sarcastic at all.

And I have a very close friend and colleague

who's a phenomenal neurosurgeon and neuroscientist

by the name of Dr. Eddie Chang.

He's the chair of neurosurgery at UCSF,

and his lab and him are expert in the study

of neuroscience controlling language and speech.

And he often tells me that he can predict,

with almost certainty,

whether or not somebody is a regular cannabis user

based, not just on the patterns of speech that they use,

but even just by recording specific neurons in their brain

that underlie the laugh reflex

and certain patterns of speech.

So this idea that cannabis use changes your ability

to speak and enunciate clearly does appear to be true.

And the stereotype that cannabis use

tends to create more of a drawl

or, if you will, a laziness in the laugh,

and some of the reflexive enunciations that people use,

does also appear to be true.

And I say all that, of course, with the caveat

that many people out there will know individuals

or perhaps you, yourselves, are individuals

that may use cannabis but that have incredible articulation,

probably better than mine

and better than other people out there

who speak for a living, so I'm not saying

that 100% of people that use cannabis regularly

can't speak well or clearly.

That's simply not what I'm saying,

and I don't want to communicate that idea at all,

but it is the case that people

who are regular cannabis users

are impacting the neural circuits involved in movement.

Movement also controls speech,

and therefore, cannabis is impacting speech.

Now I'd like to turn our attention

to whether or not cannabis can increase sexual activity,

sexual desire, and/or sexual function,

so we're going to be talking about libido, about sexual desire

and about effects of cannabis on hormones.

And while this might sound like a discussion

that's purely oriented towards recreational use of cannabis,

that is people using cannabis to heightened

or increase their sense of arousal for sexual activity,

it actually ventures into the clinical realm too,

meaning there have been excellent peer-reviewed studies

that I'll describe to you in a moment

exploring the use of cannabis or THC, more specifically,

for something called hypoactive sexual desire disorder,

which refers to a persistent or recurrent deficiency

or absence of sexual fantasies and thoughts

and/or desire for, or receptivity to, sexual activity.

This is a disorder that is fairly common,

anywhere from 6% to 9% of people, both males and females.

It used to be considered higher prevalence

in females than in males,

but now those numbers seem to be evening out.

So basically, there are anywhere from 6% to 9%

of people out there who have very diminished sexual desire.

And so, a number of those people

are interested in figuring out ways

to increase their amount of sexual desire,

and of course, there are people in the general population

who may not have hyperactive sexual desire disorder

who are interested in using cannabis recreationally

in order to increase their desire for,

or their experience of, sexual activity.

Now first we have to acknowledge

that sexual desire and activity

is a complex set of processes,

meaning it's not just one event, sex, the verb.

It involves arousal, it involves sex, the verb,

and it involves a whole set of mindsets and emotional states

that vary tremendously between individuals.

But once again, we can distill out a few basic principles,

and I should emphasize,

these are by no means the only chemicals

and neuro circuits involved in the sexual arc,

as we'll call it, desire, the act of sex, et cetera,

but they are central to it, they are vital to it.

They would be considered

what I would call necessary but not sufficient,

so there'll be other chemicals involved too,

but the main chemicals in neuro circuits

are those involved in dopamine,

so the so-called mesolimbic reward pathway,

in particular, a brain structure called nucleus accumbens,

which we'll talk about more in a moment,

is vital to all motivated behaviors and to the seeking out

of all particular types of pleasurable experiences,

and sex is no exception.

So when we hear that the nucleus accumbens is activated,

that almost always means that dopamine

has been released in that area

and other areas of the brain body,

and we can consider dopamine central

to the desire for, pursuit of, an act of sex.

In addition to that, there are molecules like oxytocin,

which are involved in pair bonding,

and they're going to be neural circuit specific

to the oxytocin circuitry,

but in terms of sexual arousal and sexual behavior,

it's really the dopamine pathway in this nucleus accumbens,

which are especially vital.

That allows us to address the question,

does cannabis increase, decrease,

or have no effect on sexual desire

and/or the ability to have sex?

And therein, we will find some very interesting answers,

and because, once again,

it will point to the fact that the effects of cannabis

on different individuals can be highly divergent,

meaning in one set of individuals,

cannabis will make them far less anxious.

And in another set of individuals,

the same strain of cannabis, at the same dosage,

will make them extremely anxious.

The same can be said also of sexual activity.

And this was beautifully illustrated

in the context of sexual desire in the journal,

"Psycho-pharmacology," in a paper published in 2017.

The title of this paper is, "Individual Prolactin Reactivity

"Modulates Response of Nucleus Accumbens to Erotic Stimuli

"During Acute Cannabis Intoxication, an fMRI Pilot Study."

So I'll give a little bit of definition

to some of the terms in the title

that will make it easier for you to understand the paper,

but then I'll just march through the results,

because they're very straightforward

and easy to understand and very interesting.

fMRI is just functional magnetic resonance imaging,

so basically subjects in this experiment

came into the laboratory.

They were either people who had not used cannabis before

or who had used cannabis before.

They were placed into a brain scanner,

one of these fMRI devices.

It looks like a tube that people are backed up into

and then they can view images in there,

and their brain can be imaged

without having to remove any skull

or drill into the skull, no neurosurgery.

The participants in this study were grouped

according to whether or not they had experienced

any aphrodisiac effects

during the intoxication with cannabis,

so that would be the first group, Group A,

they literally called it group A for aphrodisiac.

And then the second group,

and this is the only thing I don't like about this study,

is rather than call it group B,

they called them 'group non A,'

which just gets a little confusing.

So I'll try and simplify all this.

There are two groups,

and one group experiences sexual arousal

when under the influence of cannabis, THC specifically.

The other group does not.

And it turns out this is a very commonly observed divergence

of effects of cannabis.

Some people experience a lot of sexual arousal

from cannabis and THC in particular, and some people do not,

in fact, they experience suppression of sexual desire,

and it's always been a little bit mysterious

as to why that is.

Well, in this study, they showed people

in both groups erotic images,

and they measured sexual arousal

through a number of different measures.

We won't go into all that.

It was largely subjective.

There have been other studies

where they've actually measured things

like erections in males and vaginal lubrication in females,

so-called autonomic responses that people can't lie about,

so to speak, and that tap into other aspects

of the so-called sexual arousal process.

In this study, they also took blood samples

to look at the concentration of things like cannabinoids,

so this is a really nice study

in that they actually measured how much THC

was in the bloodstream in different individuals

who reacted to these erotic stimuli in different ways.

And they measured hormones, namely cortisol,

which is a stress hormone,

which tends to negatively correlate

with sexual arousal and prolactin.

And the interesting takeaway from the study was

that for people, and it didn't matter

if it was males or females, 'cause they looked at both,

for people that experienced elevated prolactin levels

under cannabis intoxication, that's how they refer to it.

People take cannabis, they measured prolactin.

Some people had elevated prolactin and some people did not.

For the people that had elevated levels of prolactin,

they did not observe activation

of brain areas associated with sexual arousal,

in this case, the right nucleus accumbens,

so you have two nucleus accumbi,

I guess they would be called, one on each side of the brain,

and the activation of that brain area

is strongly associated with dopamine and with arousal