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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology 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 so such as CBD and of course there are different types or strains of cannabis including sativa strains and indicia 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 pre-existing 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 in 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 Etc 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 Etc 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 hubman 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 anything 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 that a significant portion of the funds raised through the premium channel are going to support not just the hubman Lab podcast which we will continue to release every Monday on schedule of zero cost to all consumers content on mental health physical health and performance but proceeds from the premium channel will also be used to fund research in particular research done on human beings so not animal models but on human beings which I think we all agree as a species that we are most interested in and we are going to specifically fund research that is aimed toward developing further protocols for mental health physical health and performance and those protocols will be distributed through all channels not just the premium channel but through all channels hubman Lab podcast and other media channels so the idea here is to give you information to your burning questions in depth and allow you the opportunity to support the kind of research that provides those kinds of answers in the first place now an especially exciting feature of the premium channel is that the tiny Foundation has generously offered to do a dollar Ford dooll match on all funds raised for research through the premium channel so this is a terrific way that they're going to amplify whatever funds come in through the premium channel to further support research for Science and science related tools for mental health physical health and performance if you'd like to sign up for the hum lab premium channel again there's a cost of $10 per month or you can pay $100 Upfront for the entire year that will give you access to all the amas you can ask questions and get answers to your questions and you'll of course get answers to all the questions that other people ask as well there will also be some premium content such as transcripts of the amas and various transcripts and Protocols of hubman Lab podcast episodes not found elsewhere and again you'll be supporting research for mental health physical health and performance you can sign up for the premium channel by going to hubman lab.com / premium again that's hubman lab.com premium before diving into all of that I'd like to highlight a new what I think is very useful and zeroc cost resource this resource is what's called non-sleep deep rest or nsdr protocol I've talked many times before on the hubman 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 into a particular State and most typically that state is one of deep relaxation but also one in which you can access your bodily and brain systems for teaching yourself how to relax in real time and how to recover some of the sleep that you may not be getting at night and to restore levels of dopamine in particular areas of the brain that are involved in motivation and cognitive and motor control basically nsdr is a wonderfully restored ative tool this has been demonstrated many times over now through quality peer-reviewed science and there are neurochemical benefits and their physical benefits and their certainly psychological benefits I highly recommend nsdr to anybody that has trouble falling asleep or that wakes up in the middle of the night and needs to get better at falling back asleep as well as to anyone out there that has issues with anxiety or sort of self-regulation of any kind and if you don't have any of those issues it's also immensely beneficial just as a restorative for leaning back into Focus work of any kind now 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 zeroc 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 viran 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 yoganidra 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 included things like long exhale breathing I talk about perceptual shifts and how to move from thinking and planning to Pure sensation if none of that makes sense right now it'll be 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 especially if you didn't get enough sleep that night and you're feeling a little bit fatigued and you need to lean into the day with full Vigor you could do it at any point during the day or if you wake up in the middle of the night again this is a zero cost resource for you you can find it by going to YouTube put my last name in an 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 I'd like to thank the sponsors of today's podcast our first sponsor is levels levels is a program that lets you see how different foods affect your health by giving you real-time feedback on your diet using a continuous glucose monitor one of the most important factors in your immediate and long-term health is how well you're managing your blood glucose or blood sugar I started using levels about a year ago as a way to see how different foods and different lifestyle factors were impacting my blood glucose levels so for instance it allowed me to see how different foods and particular macronutrients and combinations of macronutrients would either Peak or trough my blood sugar or keep my blood sugar steady it Al allowed me to see how working out with weights or running how that impacted my blood glucose so for me it was a fascinating experiment unto myself as to how my meal schedule the specific Foods I was eating different combinations of food as I mentioned before and exercise we're combining to regulate this thing that we call blood sugar and that's so vital to our health I think anyone that tries levels will find that you learn an immense amount about what you're doing and what you ought to be doing differently in order to optimize your immediate feelings of well-being and your health trajectory if you're interested in learning more about levels and trying a CGM yourself go to levels. link huberman that's levels. link l nk/ huberman today's episode is also brought To Us by thesis thesis makes custom neut Tropics that are designed for your particular needs I am not a fan of the word neut tropics because neut Tropics literally means smart drugs or smart drug and frankly as a neuroscientist I know and every other neuroscientist knows that there there is no neural circuit or chemical in the brain for 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data from your blood and DNA to help you better understand your body and help you reach your health goals I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term Health can only be analyzed with a quality blood test with a lot of blood tests and DNA tests out there however an issue is you get information back about lipids and hormones Etc but you don't know what to do with that information with insid tracker they have a personalized platform that makes interpreting your data and then acting on that data very straightforward and very directed toward specific protocols what I mean by that is you'll get information back about hormone levels and metabolic factors lipids Etc and then you can look to nutritional changes supplementation changes exercise protocol changes and other lifestyle features that combine or work on their own to start to try and shift those numbers into the range that's appropriate for you if you'd like to try insid tracker you can visit insid tracker.com huberman to get 20% off any of insid tracker's plans just use the code huberman at checkout again that's insid tracker.com huberman to get 20% off and use the code huberman at checkout on many episodes of The hubman 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 or for enhancing focus and cognitive ability or for enhancing energy or adjusting hormone levels to Optimal range for you the hubman Lab podcast is now partnered with momentous supplements we partner with momentus for a number of important reasons first of all the quality of their ingredients is a exceptional it's really Second To None second of all they ship internationally and that was important to us because a number of you reside outside of the United States third we've worked with momentus very closely to develop single ingredient formulations now this turns out to be very important because if you're going to take supplements you want to know what's working for you and what isn't and of course you want to optimize the cost efficiency and the biological efficiency of those supplements to find the supplements we discuss on the hubman Lab podcast you can go to live momentus spelled o us liv.com huberman and I should just mention that the library of those supplements is constantly expanding again that's Liv mous.com huberman 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 Etc 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 a discussion about cannabis and its medicinal uses and recreational uses we need to distinguish between the sativa variety the Inda variety a variety called ruderalis that's not often discussed and hybrids of sativa indicia and ruderalis before diving into the different strains of cannabis and how they impact the brain and body 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 T THC the technical name for it is Delta 9 tetrahydro canaban 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 canabidol and canabidol 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 Etc so we've got THC CBD and also CBN or canaban 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 Etc 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 Etc 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 and 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 CB and CBN but I want to point out that the cannabis plant has over 70 70 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 Etc 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 int inging 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 indicia 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 indicia and ruderalis and for sake of today's conversation we can pretty much cross off ruderalis it's not often consumed and comp components of ruderalis are not often consumed for medicinal or recreational purposes let's focus on sativa and indicia people will consume the sativa variety of cannabis either by edible or by smoking cannabis or they will consume the Inda variety of cannabis Again by edible or by smoking cannabis or sometimes they will take it in a transdermal form or sublingual form they're bunch of different ways to get the Cannabis into the body but there's a clear distinction between sativa and Inda 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 indicia plant tends to be more short and stout and for those fanad out there I'm sure you know a lot of the other specific features of sativa versus Inda 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 you know how it affects me or affects other people for medicinal recreational purposes Well 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 because 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 you know 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 then can cross into the bloodstream and permeate throughout the body and cross the so-called bloodb 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 kind of 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 heighten levels of focus and creativity or whether or not they just perceive themselves to have heighten levels of focus and creativity the sativo 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 sort of head biased effect so uh 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 sort of head centered high alertness focus and a sense that they're more creative contrast that with the Inda varieties of cannabis and when people smoke or eat or ingest indicia varieties the psychoactive components of indica and again this is pure indicia so not hybridized with sativa at all but just pure Inda tend to lead to more full-bodied effects people report feeling more complete full body relaxation more of a stive effect Inda cannabis is often prescribed Andor 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 indicia variety is being more full body relaxation one of the ways to remember the distinction between the effects of Cannabis sativa and cannabis indicia was relayed to me by a friend who actually was a chronic meaning every day all day uh consumer of marijuana he basically smoked marijuana for 20 years before quitting about four or five years ago and he said that uh Inda is often referred to as indic couch meaning laidback in the couch um and that can help you remember that the indicia varieties of cannabis do tend to be more sedative in their effects okay so there's sativa and there's indicia 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% indicia or vice versa or 50/50 or 9010 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 is the nomenclature that's now typically used people still refer to the sativa indicia 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 indicia 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 Inda varieties again pure Inda and then you have hybrid varieties and beneath each those you have typee one type two and type three strains of indicia 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 1 piure sativa or a type 1 indicia 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 uh 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 uh you know Gene Engineering in a kind of crisper M creating mutants but literally by hybridizing crossing different plants to one another okay creating in a in a natural context the same way plants in the 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 CB or a Type 3 which is going to be very high CBD and very little THC and the same is also true for the indicia 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 kind of stimulant like effect and tends to be more of a head high if you will indicia tends to be more full body than lead to more IND the couch as I referred to it before um pun intended deep relaxation reduce insomnia Etc now within each of those sativa indicia you have type 1 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 Etc how much THC versus CBD is present and again type one is THC dominant type two of equal ratios if you will of THC and CBD and type 3 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 and acknowledge one of our sponsors athletic greens athletic greens now called ag1 is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs I've been taking athletic green since 2012 so I'm delighted that they're sponsoring the podcast fast the reason I started taking athletic greens and the reason I still take athletic greens once or usually twice a day is that it gets me the probiotics that I need for gut health our gut is very important it's populated by gut microbiota that communicate with the brain the immune system and basically all the biological systems of our body to strongly impact our immediate and long-term health and those probiotics and athletic greens are optimal and vital for microbiotic health in addition athletic greens contains a number of adaptogens vitamins and minerals that make sure that all of my foundational nutritional needs are met and it tastes great if you'd like to try athletic greens you can go to athletic greens.com huberman and they'll give you five free travel packs that make it really easy to mix up athletic greens while you're on the road in the car on the plane Etc and they'll give you a year supply of vitamin D3 K2 again that's athletic greens.com huberman to get the five free travel packs and the year supply of vitamin D3 K2 okay so somewhat surprisingly we're going to set aside cannabis we're going to take what we know about sativa indicia type 1 type two type 3 CBD Etc 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 Etc 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 would 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 one billion and probably closer to two 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 included in that list caffeine would be above all of those okay 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 listened to the episode on nicotine but even if you didn't nicotine comes from the tobacco plant and there are 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 chemical 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 etc etc 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 okay 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 canabo 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 Lian 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 lians those it 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 Etc again without ever going anywhere near cannabis we have these endogenous canabo so endogenous canabo 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 Etc they have many different effects on the brain and body we will 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 canabo receptors and lead to biological effects now it's a little bit misleading because we call them canabo receptors as 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 any 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 Etc than do our endogenous canabo another analogy that one could take in order to understand in 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 etc etc but let's just say 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 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 bodybuilding community and the sports Community they will take things like dianab ball these are modified versions of 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 supraphysiological effects effects that would essentially never be seen from testosterone that was endogeny endogenously excuse me endogenously released within the body we could say the same thing for estrogen there are estrogen receptors they bind estrogen okay but if someone were to take synthetic estrogen or to ingest a plant compound that contains various estrogen genic compounds and those plants certainly exist out there they can have super 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 right they're in our genome it programmed for it and we're born with the things and we keep these things our entire life many people mistakenly think ah you know 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 right the coming together of the chemical THC or CBD or both with these receptors is somehow supposed to happen as if this was a 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 you know edible Etc they bind to those receptors those endogenous cannabinoid receptors and they tap into into the same systems that your endogenous canabo would tap into the ones that affect mood and energy and creativity and relaxation Etc but they do so with thousandfold 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 cban 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 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 you know do as you wish right 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 clear picture of why cannabis is so effective in some contexts but also why it can create such massive suffering in other contexts because of the way that it outcompetes your own natural endogenous cannabinoid systems so let's talk about those endogenous cannaboid systems what they are and how they work because that will give us a lens into what the higher potency of Maximum Impact of the various cannabis plant varieties and strains and and THC and CBD and so forth how and why those work so what are the endogenous cannabinoids these chemical substances that everybody makes right 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 THC Etc 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 aradon glycerol aradon glycerol which we will abbreviate 2 a so let's just take eae and 2 a lump them together and talk about the endogenous canabo just to make it simple but if you want to do the Deep dive on anatomi 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 press synaptic neurons and post synaptic 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 neuro little packets those little bubbles of neurotransmitter into the gap between the pre- and post neur we call that a synaptic Clift or the synapse it's a little Gap Capal space and the neurotransmitter flows across that synapse and some of it will park in little parking spots that we call receptors on the post synaptic 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 in those neurotransmitter receptors will either cause that neuron on the postoptic side to itself relase neurotransmitter elsewhere or it will quiet it down so-called excitation and inhibition that's kind of neur 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 post synaptic side so what happens is neurotransmitter goes from press synaptic neuron to post synaptic neuron but under certain conditions the post synaptic neuron itself relases a chemical and that chemical goes backward what we call retrogradely to the pre synaptic neuron binds The receptors there and changes the probability that the presynaptic neuron will release neurotransmitter put simply endogenous cannabinoids tend to decrease the probability that the a neuron will release neurotransmitter they're sort of a break on the system they are 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 sort of a Mindbender 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 post synaptic neurons that travel retrogradely back to the Pres synaptic neuron actually can lead to strengthening of connections between the pratic neuron and the post synaptic 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 post synaptic 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 canabo can either turn up the dial or turn down the dial they can either increase the probability or de increase 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 a cross talk 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 um you know 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 they 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 on the tissues of the body including the immune system the liver even the genitals Etc 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 Etc through mechanisms that are divorced from the function of the nervous system of neurons now in reality no system of the brain 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 is CB1 receptors are mainly in the nervous system and CB2 receptors are mainly in the body and endogenous cannabinoids again eae anatomi and 2ag araido glycerol are impacting CB1 and CB2 receptors today we're mainly going to talk about CB1 receptors because they are the ones that 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 you know 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 cannaboid 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 it'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 howitz or gun like a cannon going off as compared to endogenous canabo whether or not it's eae or 2ag 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 retrograde signaling etc etc 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 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 a kind of 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 3 to 4 hours although there's some variation on that depending on individual metabolism whether or not somebody is uh familiar with the compound Believe It or Not psychologically familiar but also biologically familiar or whether or not it's a firsttime 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 it 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 say he fat they always think oh Fat's bad Fat's you know 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 Etc 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 you know how to accelerate the clearance and um I should just tell you that just losing bodily fat isn't going to um eliminate it from your system uh maybe partially in those fat cells but uh certainly in uh intrav visceral 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 okay so if someone smokes cannabis or they ingest cannabis 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 canabo receptors and impacting the signaling between neurons which leads to the subjective effects of cannabis including THC and CBD so let's talk about what those different subjective effects are again this is going to vary depending on whether or not people are digesting 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 joke intended but in any event there are exceptions but there are also general rules and the sativas tend to meet people sort of mood elevated energetic again the sort of head high and indicia varieties tend to do the opposite more of a sedative relaxant Etc why and how would they do that okay well without going into an extensive Deep dive into the different neurotransmitter systems of the brain body what we know for sure is that CB1 receptors are present on an enormous number of different neurons and brain structures and neural circuits so that the sativa varieties that act as sort of a stimulant making people feel happy because in general they do tend to elevate mood at least at certain dosages talkative uh tend to make people feel um like they have ideas that are interesting that they might want to share um tend to narrow their context so tend to increase Focus this is something is not often discussed about cannabis but it can especially the sativa varieties can increase people's level of focus to particular things that something they're watching or something they're doing or music 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 limic circuitry and other circuitry that is more stress oriented the way to think about the stress and lyic circuitry such as the amydala 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 Etc and what's happening externally and sorry to say but the default of those systems is to detect danger the sort of threat detection systems and then the prefrontal cortex largely acts as a break on those systems sort of like the rains pulling back on a Ste of horses that would otherwise just kind of take off and so the sativo varieties tend to increase CB1 activation in the prefrontal cortex and in other circuitry that then leads to a kind of overall reduction in stress because of the way that prefrontal circuitry can reduce activation of the amydala 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 will talk about the paranoid effect and why that occurs and who might predict that would occur to them in in a little bit but just want to give you a sense of how this is working because as I mentioned before THC Andor CBD are going to bind that CB1 receptor let's say in prefrontal cortex a neurons a prefrontal cortex is going to bind there and then there will 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 prefrontal cortex however at the same time the very same THC and CBD that was brought into the system system is binding the very same type of receptors CB1 receptors in other brain structures such as the amydala and causing retrograde signaling back to the presynaptic neurons in the amydala but is quieting the activation of those neurons so this is interesting right we have the same compounds THC Andor CBD brought into the body and brain findinding 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 heighten levels of alertness and activation of systems that are designed to make you talkative and alertness and mood Etc Focus or they are 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 amydala 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 you know not trivial in its own right but in terms of thinking about the creative aspects or the creativity stimulating aspects of cannabis not um sort of 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 bold face triple underline except except in some individuals depending on dosage but also depending on pre-existing neural circuitry and propensity for anxiety some people ingest or smoke sativa varieties and regardless of whether or not it's a type 1 type two or type three variety okay 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 kind of what I would call Street lore or dorm room lore or kind of um peer P not peer reviewed uh but uh sort of peer discust I mean among friends and people and acquaintances lore out there that what one needs to do is simply smoke more right 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 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 strainer 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 H 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 you know between 5' 7 and 6 feet tall and uh you have blue eyes uh or brown eyes that the sativa varieties are going to be right for you or that the sativa varieties are going to give you panic attacks I can't do that the only only way to determine it would be to actually experience ingesting those or smoking those which is certainly also not what I'm suggesting right 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 of or generally leads to one specific set of effects height and focus mood Etc whereas when they ingest or smoke indicia and its components right again we're still talking about THC and CBD in varying ratios but now indicia cannabis and you say well why would it improve the transition time to sleep or at least give people the impression that it improved the transition time to sleep we'll talk about what Indica actually does for sleep in a little bit but indicia also tends to suppress activation of the amydala and threat detection centers in the brain again binding the same CB1 receptors and those retrograde signaling mechanisms I talked about before but it also tends to shut down the hippocampus an area of the brain associated with memory which is why indicia varieties lead to pronoun Ed 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 break on particular biological mechanisms and there are going to be a constellation of different accelerations and breaking of different neural systems in the brain and body depending on whether or not people ingest sativa or indicia 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 and 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 right because there can 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 smokable forms of cannabis especially if those smokable forms of cannabis are obtained through sources where there isn't a lot of clear information about the total amount of THC in that product now this is all changing quite a lot nowadays because of the commercialization 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 well-being pain relief Etc or whether or not they have full-blown panic attacks Etc is very hard to predict based on dosage information alone now of course we can create broad categories and we're going to talk about studies that create broad categories of low dose moderate dose and high dose frequent use and infrequent use but unlike alcohol unlike nicotine we can't really point to 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 you know how often can they smoke cannabis or how often can they eat cannabis or THC or CBD and 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 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 def osit 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 okay hippocampus means seahorse it's shaped like a seahorse anatomist 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 indicia 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 Ina 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 Inda varieties are often used for relaxation and for promoting sleep regardless of whether or not sativa or indicia variety and again regardless of the ratio of THC to CBD there is a general suppression of neural circuits within the so-call basil ganglia and cerebellum basil ganglia and cerebellum are areas of the brain that are involved in action planning and withholding action so that would be the basil ganglia So-Cal go noo 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 rening 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 sort 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 increas 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 aru 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 and anticipation of taste as well as the experience of taste so the narrowing of focus to what you want to go eat right you really crave I don't know 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 okay 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 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 anti-os acceptive 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 what 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 Etc 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 lowd 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 uh cannabis most Studies have not distinguished between sativa and indicia strains and that's unfortunate because in the real world people are distinguishing between sativa and indicia strain in their patterns of use and what they prefer and what they don't prefer 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 has 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 I mean what are they trying to achieve is it always about not feeling pain is it always about reducing anxiety well sometimes it is but often times 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 uh in terms of Technology development and uh culture and music and poetry Etc we really can look to creativity as the state that fostered so much of that Evolution so whe 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 right so the painting that you paint in the creative state hopefully is a painting that still inspires and um 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 right here we are as as 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 uh the person in the room who's listening to all the IDE ideas and taking them all in maybe it's a a panel of you know how should we um you know how should we get a certain product out to Market or you know what are the what are the different motifs that we should include in a piece of music or you know um what should we do in terms of re rearching 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 all of the ones that they heard okay 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 kind of braiding them through and trying to get some common theme 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 okay so these are similar in related but typically the creativity process involves first brainstorming and Divergent thinking and then in order to arrive at something to actually create something right 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 of literature a specific scientific project or experiment and so on that usually involves conversion 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 neural circuits and neurochemicals convergent and Divergent thinking we can arrive at a 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 nerv nervous system excuse me such as bipolar disorder which we've done an 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 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 Etc 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 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 that sometimes even seem a little disconnected some people might think of this as kind of attention deficit but it's not it's really the idea of you know throwing out disperate ideas right um you know you hear sometimes you know you throw things against the wall and see what sticks well these people that's a obviously an analogy but people are um 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 kind of an inverted u-shaped way for those of you that are watching on YouTube I'm just drawing kind of a 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 level lels 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 kind of 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 away that then you eventually Converge on some new product New Idea new song Etc 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 a arguably a very reductionist view we're looking at all of this thing of we're calling creativity through a very neuroscienc 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 kind of a joy or relation 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 right you're not accepting all of them as true and valid and interesting and combining them but there's this idea that you know it's 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 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 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 homing 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 itre 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 okay so cannabis increases dopamine in these areas Elevate 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 the study um first author is Emily lefrance and the title of the paper somewhat amusing uh in its own right which is it starts with a question uh inspired by Mary Jane of course Mary Jane being one of the kind of old school versions of 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 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 fluence 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 all the Cannabis users are are 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 it turns out that one of the major ways in which it was accomplished is that cannabis users even if they are not under the influence of cannabis are far more open to novel ideas and they have a more explorative and sort of reduced anxiety or I should say lower anxiety mode of thinking when they explore novel ideas which is essential for Divergent thinking so they observe 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 are associated with creativity but rather are 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 right 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 uh 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 spous correlation meaning that it's not the case that cannabis increases creativity but and I in I inserted the 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 convergent thinking and creativity that 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 that complex signaling stuff you can imagine that there will also be other studies and in fact there are where Divergent and conversion 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 the 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 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 Etc 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 heighten levels of relax ation and reduce 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 their changed patterns of speech in fact there's a kind of 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 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 SPL hairs and say well what what if somebody uses it twice a month well listen uh the clinical literature and the scientific literature don't get that specific and of course there are an infinite number of ways to arrange one's uh 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 qu chronic use Excuse me that or more can be anywhere from twice a week to every day to just in the evenings Etc 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 when under the influence of cannabis and when not under the influence of cannabis if they are 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 and 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 we will provide a link to that first author Adam vogle really like this um 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 cannabist use have altered speech production uh tells you pretty much everything you need to know except there's important Nuance in here because as I mentioned earlier people who smoke sativa varieties of cannabis often times will become more talkative much more talkative however whether or not people tend to rely on sativa cannabis use or indicia 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 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 Inda varieties of cannabis impact those brain centers involved in movement the basil ganglia remember the go no-o 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 indicia variety there are disruptions in motor circuitry and as you may have heard if you listen to our episode with Rockefeller Professor Dr Eric Jarvis who works on speech and movement speech is movement right 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 Eric 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 you know fancy nerd speak for looking at how much inflection there is or looking at how long people hold vowels or consonants Etc 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 canab causes on our patterns of speech well the first one is a change in what's called spectral tilt and that's fancy nerd speak for vocal effort and intensity so I'm not a pot smoker I confess um 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 and intensity and might say spectral tilt is vocal effort and 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 a pro IM 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 they're in and listen 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 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 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 cannabis marijuana is the most commonly used elicited drug but frankly that would have 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 sort of 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 do have the really drawn out kind of N and often times this will be detected in the laugh you know there's this sort of stereotypical Stoner laugh as it sometimes called rather than say or that's a fake laugh obviously um it's hard to make myself laugh if something's not actually funny enough to think of something funny when people say like that's a bit more of the way I might laugh like sort of the inspiratory laugh um or the which is expor laugh people who use cannabis chronically will often do the right which is sort of the back of the throat it's sort of this the um it's neither inspetor nor expor laugh and believe it or not there's an entire literature on inspetor inhaling versus expor laughs and there's also a literature on cannabis altering the pattern of inspetor and expor 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 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 underly the laugh reflex and certain patterns of speech so this idea that cannabis use changes your ability to speak can enunciate clearly does appear to be true and The Stereotype that cannabis use tends to create more of a draw or kind of a um 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 in heighten or increase their sense of arousal for sexual activity it actually Ventures into the clinical realm too meaning there have been excellent pure 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 Andor 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 neural circuits involved in the sexual Arc as we'll call it desire the act of sex Etc but they are to it they are vital to it they would be considered what I would call necessary but not sufficient okay so there'll be other chemicals involved too but the main chemicals and neural circuits are those involved in dopamine so the so-called molic 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 and body and we can consider dopamine Central to the desire for pursuit of and act of sex in addition to that there are molecules like oxytocin which involved in parir 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 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 psychopharmacology in a paper published in 2017 the title of this paper is individual prolactin reactivity modulates response of nucleus accumbent to erotic stimula during acute cannabis intoxication an fmri pilot study so I'll give a little bit of um 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 are 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 on um 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 aphrodesiac effects during the intoxication with cannabis so that would be the first group group a they literally called it group a for aphrodesiac 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 Nona which is uh 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 the sort of so-called autonomic responses that people can't lie about um 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 CU 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 some people did not okay 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 accumbent so you have two nucleus aumi I guess they' be called one on each side of the brain and the activation of that brain area is strongly associated with dopamine and with arousal and sexual arousal in particular in this study and if people had elevated prolactin they did not experience activation of nucleus accumbens and they did not report feeling sexually aroused to those pictures at least not to the same degree as the other group so some people's prolactin levels go up when they ingest cannabis and those people do not achieve elevated levels of sexual arousal when under the influence of cannabis even if they're looking at erotic stimuli that makes sense because prolactin is mutually inhibitory as we would say it's kind of in a push pull with dopamine when dopamine levels are high prolactin levels tend to be low and when prolactin levels are high dopamine levels tend to be low the other group so-called group a that experienced elevated levels of sexual arousal when under the influence of cannabis and viewing erotic stimuli that group did not show elevated levels of prolactin in response to cannabis so this I believe resolves a long-standing controversy in the field which is does cannabis increase sexual arousal well it depends if you fall into the category of person who has elevated levels of prolactin in response to cannabis then no actually cannabis will suppress your sexual response and desire if however you are in the category of person that does not have elevated levels of prolactin in response to cannabis well then erotic stimula can potentially and in fact do increase sexual arousal in the majority of individuals now many of you are probably hearing this and wondering whether or not you fall into one category of individual or another and the key thing here to understand is that levels of prolactin heading into the study did not predict did not predict whether or not people would respond to cannabis with elevated or non-elevated or even reduced levels of sexual arousal it was whether or not people's prolactin levels went up or did not go up that predicted whether or not their levels of arousal would go up or not so if you are somebody who yes does experience elevated levels of sexual arousal and function when under the influence of cannabis then it's very likely that cannabis does not increase your prolactin levels at least not to a significant degree while you're taking it and if you are somebody who does not experience increases in sexual arousal or function or even diminished sexual arousal and function when under the influence of cannabis it's very likely the Cannabis is increasing your levels of prolactin unfortunately there's no way to know or predict based on some other measure I think the outcome measure that is increased or not increased or even reduced sexual arousal is really the litmus test by which one can figure that out while we are on the topic of the effects of cannabis on sexual function and hormones like prolactin it's probably worth mentioning the Cannabis has been studied extensively for its impact on other hormones and we can summarize those literature in the following way and here I'm referring to studies only on adults we'll talk about the developing brain and body in a little bit but it is very clear that smoking cannabis increases prolactin levels very very clear now you might say I didn't you just describe a study about a set of individuals whose prolactin didn't increase and as a consequence their level of sexual desire went up yes there are a subset of individuals for which that's true but people who smoke cannabis do experience increases in prolactin and that's especially pronounced in people that smoke cannabis more than twice a week so this is important prolactin as I referred to earlier is reciprocal or mutually inhibitory with dopamine one way to think about this is in the context of the normal sexual arousal Arc whereby dopamine is increased when people are sexually aroused but then after orgasm both in males and females prolactin levels Skyrocket this is actually what creates the so-called refractory period for males during which they cannot achieve erection again for some period of time that relates directly to how long long the prolactin increase lasts okay prolactin is also increased in new parents of all species including humans which at least partially explains some of the reported or typical reductions in sexual desire and activity in new parents now there are other reasons for that too sleep deprivation but nature is smart and has arranged a set of hormones and circuits in the brain and body such that when tending to a newborn is the most important thing it relegates it reduces the importance of producing more children and sexual activity in those moments and days and weeks sometimes longer so when prolactin levels are up dopamine levels are down smoking marijuana more than twice a week significantly increases prolactin there are fewer studies exploring whether or not edible marijuana has the same effect although the preliminary evidence suggests that it does not get into this in a lot more detail in a future episode all about hormone with Dr Kyle Gillette who's been on this podcast before but he verified that and my read of the literature is that the edible forms of marijuana cannabis probably again let's put an asterisk next to this but it appears do not have as much of a prolactin elevating effect and therefore not as much of a dopamine suppressive effect and therefore not as much of a testosterone suppressing effect and that gets the issue of testosterone does cannabis marijuana suppress testosterone and this is a very controversial literature and here's why some studies say yes it suppresses testosterone in males and females and keep in mind that testosterone and females is vital for libido and cognitive function cellular repair Etc so it's not just important in males of course however other studies say that cannabis does not decrease testosterone and it seems to depend on whether or not the Cannabis is brought into the system by way of smoking or edible and it seems to depend on whether or not the Cannabis is used chronically by an individual or acutely and here I just want to zoom out and say that studies on cannabis or drugs of any kind in humans are really complicated if you think about it someone has to come into the laboratory and let's say you want to study chronic cannabis use well you can't keep them in the laboratory all the time so you have to rely on their self-report of how often they use cannabis and in what form and you can't really control from one individual to the next of how much cannabis in THD bring into their system one person might smoke cannabis out of a bong and take big deep you know lungs full bong inhalations or such other people might smoke joints other people might use Edibles it becomes very complicated to know what people have done and that they're reporting it accurately and no joke here especially if marijuana is impacting the short-term memory systems they might not actually remember they might not be tracking it that well contrast that with studies of the acute use of cannabis and THC where people who are not regular users come into the laboratory and now suddenly with institutional guidelines and safety Protocols are under the influence of THC in cannabis well now you're dealing with a person who may not have experience with the elevated heart rate and blood pressure that's characteristic of cannabis because it is a stimulant at least when initially brought into the system even if it might eventually lead to relaxation so now you got someone who's anxious or somebody who's not anxious who's deeply relaxed and you're trying to study these effects so it's a it's a moving Target of sorts it's very complicated to study marijuana and cannabis and its various derivatives in this way now you can probably appreciate better as to why there's so little Nuance data about sativa versus indica versus different ratios of CBD and THD it's really difficult to do these studies in the first place that said the general rules are smoking marijuana increases prolactin in men and women which will reduce dopamine and testosterone smoking marijuana chronically meaning more than twice a week does appear to reduce testosterone significantly and Elevate so-called aromatase enzymes which are the enzymes that convert testosterone into estrogen this might partially explain the effect that occurs in about 35% of males which is gynocomastia which is a development of breast tissue in males in particular young males who have elevated levels of testosterone or who are taking exogenous testosterone for testosterone replacement therapy or if they're taking high doses anabolic steroids or or in females the increase in breast size which is due to additional estrogen from testosterone converted to estrogen so it does appear that marijuana and cannabis increase estrogen reduce testosterone increase prolactin especially in chronic users now I'm sure that some people out there will say well their testosterone levels are exceedingly high or they are fine meaning the constellation of symptoms associated with low testosterone and Elevate estrogen are not present in them that probably means one of two things or both they either had elevated levels of testosterone to begin with so their ceiling was higher so bringing it down didn't have that much of effect or that they have very low levels of aromatase in their system there some anecdotal evidence that smoking particular parts of the marijuana plant in particular the seeds can increase Aroma taste and the conversion of testosterone to estrogen I think in the old days the lore was the seeds make you sterile and I think that was related to what I just told you this increase in conversion of testosterone to estrogen there's a vast literature on the effects of cannabis on fertility it does seem yes it does seem to alter sperm motility and sperm health and function when taken chronically more than twice per week in particular high doses of high potency THC this is something we will cover in far more detail on a future episode all about fertility and in females there's an increase in estrogen as a consequence of smoking marijuana and increasing prolactin and estrogen in parallel whether or not that's detrimental isn't clear although I point out that elevated estrogen and prolactin can be Associated again can be Associated not necessarily and certainly not causitive but can be associated with elevated levels of or frequency of breast cancer detection so cannabis and its effects on hormones are not without consequence there are effects of cannabis on cortis ol in some individuals it greatly increases cortisol due to the anxiety and paranoia it can create and in other individuals it reduces cortisol again we have these Divergent effects but I want to be very clear the effects on prolactin meaning elevated prolactin the effects on testosterone meaning at least most studies point to reduced levels of testosterone and increased estrogen that seems to be true for most all individuals that chronically use cannabis whereas the effects on cortisol tend to be Divergent cannabis increases cortisol in some individuals and decreases cortisol in others in general increases in cortisol that are ongoing are not healthy for us and so on and then of course there are other effects on hormones and I'll just Briefly summarize those that THC in particular not CBD but THD in particular is known to be strongly inhibitory for something called gatot tropin releasing hormone this is a hormone that's released from the brain from the hypothalamus that then feeds onto or I should say signals to the pituitary gland which is also near the roof of your mouth a lot of stuff happening near the roof of your mouth it turns out biologically and reduced levels of gonadotropin releasing hormone caused by cannabis use reduce levels of LH gluenz hormone and FSH which reduce levels of testosterone and sperm production in males and egg health and ovulation and menstrual function in females now I'm sure there are a number of women out there who will say they have perfectly normal menstrual cycles despite using cannabis I'm certainly not going to dispute that but if you are somebody who's trying to maximize fertility or regulate or balance hormones marijuana and cannabis reduces G&R that is the gatot trop and release from the hypothalamus and thereby reduces luteinizing hormone and follicle stimulating hormone which are released from the pituitary and travel in the bloodstream to support normal ovarian function and health and normal testicular function in health in female and males respectively up until now I've been discussing the biological and psychological effects of cannabis now I'd like to shift our attention to some of the negative health effects of cannabis and shine light on some of the individuals or groups out there that need to be especially wary of and probably avoid cannabis use entirely including ingestion of cannabis by way of edible and I frame things that way because I think there is an increasingly large number of people out there that appre appreciate that smoking tobacco or smoking cannabis vaping tobacco yes vaping tobacco or vaping cannabis each and all have negative Health consequences on the lungs and on the so-called endothelial cells of the body the cells that make up the vasculature the capillaries and blood vessels if you don't already know this I'll make it very clear and I'll make it very brief whether or not you smoke or vape to tobacco or cannabis you are severely impairing the function of endothelial cells that make up the capillaries and blood vessels of your brain and body and that is known to decrease cognitive capacity over time increase probability of Strokes severely impact lung function and also lead to things like peripheral neuropathies it leads to sexual dysfunction because of lack of blood flow to the genitals can lead to other aspects of reproductive damage including to the ovaries and testies essentially there is no other way to State it except that smoking and vaping have negative Health consequences that are independent of the substances that people are trying to get into their bloodstream by smoking or vaping so people smoke and vape tobacco and people smoke and vape cannabis and in both cases if we just set aside the Direct effects of tobacco and the Direct effects of cannabis we can confidently say that the process of smoking of inhaling smoke into the lungs and yes also vaping bringing the chemicals that transport nicotine or in this case cannabis into the lungs by way of vaping are both severely detrimental to endothelial cells I think a few years ago when vaping wasn't as prominent there was this question and this idea that maybe vaping was going to be far healthier or at least not as bad as smoking but now we can see a huge number of negative health effects of vaping some of which are distinct from the effects of smoking so if you'd like more information on smoking versus vaping please see the episode that I did on nicotine we will also do an entire episode all about vaping in the future but there's really no way to slice it and dice it or candy coat it the fact of the matter is that smoking has clear and severe negative Health consequences regardless of whether or not you're smoking tobacco or cannabis THC and vaping has negative Health consequences whether or not you're using the Vape to bring in nicotine or THC or some combination of THC and CBD that's simply the way it is with that said now I'd like to focus our attention on the Direct effects that cannabis has either by way of THC action or by way of CBD action in terms of positive or negative health effects on the brain and body and we're going to explore that first as a a function of age and the reason we're going to do that is related to a fact that I mentioned at the beginning of the episode which is that the CB1 and the CB2 receptors the two receptors for cannabis to which THC and CBD and CBN and all other psychoactive compounds and cannabis bind to to have their actions are present throughout development believe it or not they are present very soon after conception and the CB1 and CB2 re ctors actually play a critical role in the development of the fetus now you might wonder why that is because of course the developing fetus doesn't necessarily expect to see cannabis or to be exposed to cannabis THC and CBD but as you recall endogenous cannabinoids are present in the adult brain and body and endogenous canabo it turns out are also present in the developing fetus in fact endogenous cannabinoids are present at much greater levels in the developing fetus than they are after a child is born and levels of endogenous canabo actually go down across development I find this really interesting what this means is that endogenous canabo and activation of the CB1 and CB2 receptors are an integral part of neural development and this is going to become especially relevant in considering whether or not pregnant mothers should or should not use cannabis or CBD and it also points to some very interesting biology in terms of how the brain develops and how the body develops now the development of the brain and nervous system and body is a fascinating and vast literature certainly far too vast to cover in today's episode especially at this late hour as it were but we will have a future episode all about brain development in terms of the effects of cannabis it's sufficient to say that cannabinoid receptors are present and active in the developing fetus they are present and active in the newborn they are present and active in adolescence and across that time from conception until adolescence endogenous canabo are mainly responsible for the actions of those canabo receptors during that time the cannabinoid receptors are having very specific effects that are distinct from their effects later in life and those effects can largely be explained in terms of neural development again we don't have time for an entire lecture on this now but during development your body was a collection of a bunch of cells it's actually called a blastula which means a ball of cells and then those cells actually have to grow out connections and duplicate themselves and this is a very interesting process by which neurons initially are situated far apart and then they grow out connections and make contacts with one another they remove certain connections depending on what kind of Life events you're exposed to if you have a wonderful event early in life or a traumatic early life those connections change Etc the important point for to today's discussion is that the CB1 receptor in particular is expressed on every neuron in the developing brain and has been shown to be important for every aspect of neural development from the proliferation of cells meaning getting enough cells to create a brain to the outgrowth of the so-called axons the little wires that connect up neurons with one another to the steering the direction that which those axons go in development which is essential and even so far as to explain the connections that form between neurons the so-called synapses and then how those synapses work so the basic statement here is that endogenous cannabinoids and cv1 receptor activation are critical for every aspect of brain wiring and development with that in mind the statement I'm about to make is absolutely terrifying at least to me and frankly it should be terrifying to you as well and the statement is the current statistics on cannabis use in pregnant mothers is absolutely shocking the most recent survey of pregnant mothers in the United States show that 15% 15 15% of pregnant mothers report using cannabis in some form or another either smoking it or more likely ingestion of an edible because they are aware of the negative effects of smoking on the developing fetus ingestion of an edible to increase THC Andor CBD during pregnancy which to me I have to say as a developmental neurobiologist is frankly it's a it's scary it's absolutely scary because that CB1 receptor is not just a minor player in neural development it is absolutely Central to every critical aspect of brain wiring and development now the long-term implications or even the short-term implications of this 15% of mothers self-reporting the use of cannabis at some point during pregnancy are not yet known this is as we would say an experiment that's ongoing but I'd be remiss if I didn't point out these data and just implore you please please please if you are pregnant or considering getting pregnant you're a cannabis user whether or not you're using Edibles if you're a CBD user please do whatever is necessary to not ingest cannabis or smoke cannabis or ingest CBD during pregnancy now there may be certain clinical indications by which your physician and your OBGYN and your the pediatrician that will eventually be the pediatrician for your your child will prescribe CBD although it's hard to imagine what those are I contacted a number of different pediatricians and OBGYN and not a single one said they would ever suggest and in fact would strongly discourage their patients from using cannabis during pregnancy but I think that the Advent of edible forms of cannabis and and the combination of THC and CBD in certain products and the fact that most people view CBD as safer because it does not include as or does not have I should say the psychoactive effects that THC does has led to a situation where where you have 15% of pregnant mothers using cannabis at some point during pregnancy and maybe even frequently throughout pregnancy and the effects on the developing fetus are completely unknown but recall that cannabis and THC and CBD out compete meaning they Park in the receptor for endogenous cannabinoids and prevent endogenous cannabinoids from having their normal level and pattern of action so this is absolutely critical I cannot encourage you enough or rather I should say I cannot discourage enough the use of cannabis and any related compounds in cannabis edible or smoked certainly not smoked but even edible during pregnancy and certainly in breastfeeding lactating mothers the same is also true recall that cannabis and THC and CBD are incredibly lipophilic they they are fat soluble and they get into cells ve very readily and they cross the blood brain barrier they cross the blood placental barrier so when I encountered this statistic I I had to kind of wipe my eyes a few times I could not believe it and yet I crosschecked that number with a few other studies a few others have come in a little bit lower at you know somewhere like 13 to 14% And a few have come in a little bit higher but the average of 15% is both striking and shocking so I don't know how to make the message more clear I hope that is clear please do not use any cannabis THC or related things including CBD smoked or edible if you're pregnant lactating Etc now we are at the point where we need to consider some of the negative health effects of cannabis that have been well documented in peer-reviewed studies and before I do this I want to return to a point that I made earlier which is that nothing I am about to say relates directly to issues of legality if we consider alcohol for instance alcohol is legal in most areas of the world it's certainly legal in the US and yet there's an age limit for its use typically it's not available to people until they're 21 or older it's not to say that certain people don't use it before age 21 but it's not legal it is illegal to buy or possess alcohol consume alcohol before age 21 and I think with good reason because the brain is still developing likewise we can have a informed discussion about cannabis and its various components that can fully acknowledge the reality which is that one of the major harms of cannabis in the past has been the legal ramifications of cannabis being illegal I that's a statement that is no longer controversial and this is not a discussion about legalization ation or non- legalization if you look to the scientific literature the epidemiological literature there are wonderful data out of Carlton University and elsewhere in Canada showing that you know many of the negative effects of marijuana and THC are due to the criminal justice system itself that is the creation of illicit drug businesses the creation of organized crime the creation of a number of different features related to the illegality of cannabis and again this isn't the topic of today's episode but that should be acknowledged and at the same time we need to acknowledge that when a compound a drug or whatever you want to call it becomes legal there's a tendency to assume that it's safe and safe for everybody and with respect to cannabis and THC and perhaps even CBD but certainly for THC and cannabis that's smoked or Vaped or consumed in edible form that is simply not the case there are clear data pointing to negative health effects of cannabis use and THC use which again is not to say that there are not positive effects on mood anxiety pain relief etc those are out there and they exist and we will mention some of those of course and we've talked about some of those creativity for instance Etc but if we do not acknowledge the negative health effects that are documented in the literature then we are overlooking some very important data especially as it relates to the development of psychosis in certain individuals so with that said there are very strong data and I will provide links to these resources pointing to the fact that for people who are chronic users of cannabis that is using it twice a week or more that over time their levels of anxiety actually increase and this is true even for individuals that are using strains of cannabis that while under the influence of cannabis reduce anxiety over time meaning over the course of 12 or more months there is a well documented effect of the anxiety relief that cannabis and THC initially brought being less and less potent that is people need to smoke more of it or ingest more THC in order to achieve the same level of anxiety relief and in some cases a switch from anxiety relief to increase in anxiety and again that's increasing anxiety not just when the drug is not being consumed but also while under the influence of the drug why would that be we have to go back to our understanding of the CB1 receptor and the potency with which THC binds to that CB1 receptor when THC is brought into the system over and over again meaning twice a week or more The Binding of THD that CB1 receptor eventually causes is a sort of habituation or attenuation of the entire process of binding the receptor and creating the psychoactive effects so initially it creates anxiety relief but over time the affinity for the receptor doesn't change meaning it can still park in that slot with a lot of affinity a lot of strength but there are few fewer receptors available and then the signaling that's Downstream of those receptors becomes less and less robust now this is a topic we didn't get into in too much detail today because I didn't want to include even more biological detail but the CB1 receptor is a so-called G protein coupled receptor it that's a mouthful But A G protein coupled receptor basically is like a Bucket Brigade so while some receptors in the brain and body are such that when something a chemical binds to them that receptor has a direct action like it opens and allows stuff to rush into the cell increases the excitability of the cell so calleded fast effects these G protein coupled receptors and CB1 is a gep protein coupled receptor they are more like a Bucket Brigade where they kick off a process through one molecule that then is handed off to another molecule that this then is handed off to another molecule it's a long chain or Cascade of events that whose long chains or Cascades of events have a lot of opportunity for regulation for adjustment you know receptor systems in the brain and body especially receptor systems like the cannabinoid system that are used to being kind of tickled not punched you know tickled by IND enous cannabinoids every once in a while some binds has an effect but certainly not bound with Incredible potency and over and over again as they are when THC is coming into the system well those systems eventually over time they adjust themselves so that the body and those cells can achieve so-called homeostasis so when people are using THC more than twice a week what ends up happening is those G protein coupled receptors in the downstream signaling mechanism start to adjust themselves and it requires more more and more drug so either higher dosages or more frequent use and a lot of the positive effects the so-called decrease in anxiety increase Focus increase creativity some of that starts to WAN it starts to dissipate and people wonder why they have to use so much cannabis just to achieve a fraction of the effect that they used to be able to achieve with even a lower dose so anxiety is getting worse over time and that's anxiety during the drug use and outside of the drug use some people work around that or try to work around that by using varying strains of cannabis or changing the pattern of delivery from you know smoking to vaping or from vaping to edible and from edible to transdermal anyway they go through a lot of gymnastics and writhing and um seeking but nonetheless anxiety increases over time also it's very clear that depression increases over time and especially this is surprising to me but especially for individuals that were not depressed at the outset of their use in other words they didn't start using cannabis because they were depressed but rather the depression starts to emerge as a consequence of the Cannabis and THC use so that's serious in fact we now know based on really solid epidemiological evidence that depression is not a strong predictor of seeking out cannabis it doesn't drive terribly many people to seek out cannabis use but cannabis use itself makes people four times likelier to develop a chronic major depression so anxiety is increasing depression is increasing and this turns out to be especially relevant important to young people why do I say that well if you look at the data and again I think some of the strongest data or data to come out of the Canadian system they've done some really beautiful controlled studies I really hope to invite some of the uh people who arranged and ran those studies as guests onto the hubman Lab podcast but if you look at the data out of Canada or you look at some of the data out of Northern Europe and the US what you find is that the probability that somebody will use cannabis and then go on to use it chronically correlates very strongly with age so for instance some of the highest degree of cannabis use is among individuals 16 to 24 years old in fact in individuals who are 16 to 24 years old and in particular in students and people who are working surprising more than in unemployed populations being young 16 to 24 at least to me that's young and being a student or working doubles the likelihood that somebody is going to use cannabis on a regular basis twice or more per week the typical age of initiating cannabis use nowadays is about 19 years old so 18.7 and about 20% of people in that age bracket of 16 to 24 years old are using cannabis daily either by vaping by smoking or by edible that's an enormous number at least by my read it's an enormous number and here's why it's a really serious concern during the ages of 16 to 24 The canono receptors are still available they are not being as strongly driven by endogenous cannabinoids but by ingestion of THC and or CBD there are Downstream effects on the signaling with in those cells that all the data point to creating a much much higher likelihood of developing major depression severe anxiety or psychosis at later ages so to be very clear cannabis use between the ages of 16 to 24 in both males and females is increasing anxiety increasing depression in the immediate years and within the one year's time or so so much so that people are using the cannabis ongoing in an attempt to reduce that anxiety and reduce that depression but in addition to that the cannabis use and because of the signaling mechanisms involved are predisposing those individuals to psychosis later in life if you look at individuals who start using cannabis even younger age 14 or even as young as 12 the probability of psychosis later in life in particular schizophrenic or schizophrenic like episodes more than doubles so this is a really serious concern and this is completely aside from any so-called positive effects or beneficial effects of cannabis that people might derive from occasional use as adults meaning people older than 25 so for the person who's older than 25 who you know eats an edible every once in a while or who smokes cannabis every once in a while and you know people love to make the argument you know it's not as bad as alcohol right which I frankly is a terrible argument because if you saw our episode on alcohol alcohol is pretty bad um but even so it's just not a good argument you know saying that something is good because it's not as bad as something else is simply just not a good or valid argument at least not biologically speaking um the use of cannabis in young populations is very strongly predisposing people to psychotic episodes and we know the mechanism by which this occurs this is occurs by a thinning of the so-called gray matter and it's called gray matter because with neurons nerve cells they have a so-called cell body that's the part that contains the DNA and manufactures all the neurotransmitters Etc and those are shipped out to the other parts of the neuron that include the axon the wires between axons and those axons under the microscope because they have a lot of fatty tissue around them and this is healthy fatty tissue that allows electrical transmission to be fast that fatty tissue th Those portions of the cells are called white matter so you have gray matter and white matter gray matter are the so-called cell bodies where the DNA and all the stuff is manufactured White matter are the sort of the axons or the wires through which all the key components are shipped out to the synapse Etc wonderful data and I do say wonderful because this is part of a large-scale Consortium and we will provide a link to the paper this was publishing trans translational Psychiatry just this year point to the fact that adolescent cannabis use accelerates the thinning of the prefrontal cortex and the gray matter in particular so what this means is while during normal development the gray matter the prefrontal cortex and all the cells there are indeed intended it's a normal process for it to thicken and then thin a little bit as connections are adjusted and people learn and mature and grow up this is part of the normal healthy maturational process independent of cannabis use when kids because these really are kids use cannabis and it doesn't matter the mode of cannabis delivery whether or not it's vaping or smoking or edible that gray matter thins at a a much much greater rate and the reason I like this paper publish in translational Psychiatry this year so much is that they link the amount of cannabis use heavy moderate light or no cannabis use to the rate of prefrontal cortical thinning and it's absolutely clear from these data that the more often young people meaning individuals between the age of 14 and 25 the more often they consume or smoke or vape cannabis the faster and the more extreme that cortical thinning is and the cortical thinning is incurring in exactly the area of the brain that's involved in planning in control over one's emotions in reflexes in organizing one's life in a number of different ways anywhere from cleaning one's room literally you know knowing what goes where to making plans that extend out through the day through the week through a year essentially becoming a functional human being involves using your prefrontal cortex in a variety of different contexts and different sort of time domains the time domain of an hour the time domain of a day making plans and being able to execute plans is fundamental to being a healthy human being and it's absolutely clear from these data that the more cannabis one uses the more impaired those neural circuits are they simply no other way to to view these data in fact so much so that even small amounts of cannabis use are associated with rates of cortical thinning and degrees of cortical thinning that are really detrimental and concerning for normal cognitive processes if you were somebody who smoked marijuana or consumed cannabis in any form or another during adolesence does that mean that your prefrontal cortex can never be rescued that it can't come back well the short answer is it probably can be rescued to some degree it will depend on how much cannabis you were using and how often and what strains of cannabus Etc there's really no traveling back in time as my graduate advisor used to say you know time machines are broken at least for now we don't have time machine so all you can really do is try and emphasize first of all quitting cannabis in any form and focusing on behaviors that emphasize endothelial cell blood flow Health to the brain so that would be cardiovascular exercise adequate nutrition not smoking nicotine and there are a number of other things that one can do we will do an entire episode all about trying to reverse the effects of cannabis and Other Drug use dur adolescence we don't have time to do a deep dive on that right now but all the things that standardize and kind of promote Health adequate sleep uh good social connection regular cardiovascular and weight training exercise Healthy nutrition and what that represents to you healthy metabolic function and weight etc those are all going to facilitate some recovery of brain function in particular prefrontal cortical function by way of all the positive effects that those behaviors and choices have but with that said if you are in the age bracket that I've been referring to this 14 to 25y old age bracket and you are a occasional even or chronic cannabis user you should be very very careful and concerned about the long-term effects that potentially have that statement is bolstered by another statistic which is that unlike a lot of other drugs the rate of cannabis use is strongly related to how dangerous people perceive cannabis to be now that might seem obvious on the one hand you know if you think something is very very dangerous you would expect that the probability that somebody would use it would be very very low and if they think something is safe the probability would be high but that isn't necessarily the case if you think about it cannabis is a unique instance in which nowadays we are hearing yes it's becoming legal in a number of areas and we talked earlier about why that's probably a good thing in most circumstances but that we aren't just hearing that cannabis is safe or it's not just being implied that cannabis is safer but many more people are talking about the positive effects of cannabis without a lot of discussion about the negative effects of cannabis and I realize that saying this is going to upset some people out there because I know that there are a number of people who fought very hard for the legalization process and I want to acknowledge that I also want to acknowledge the many known positive effects of cannabis in adults with very occasional use provided it is delivered safely and in the safe context and setting and with legality that is entirely distinct from the issue of whether or not cannabis is safe for the developing brain and body again I'm not demonizing anybody for using cannabis but I want to make the point very simply and very directly it is far in way a different circumstance for the brain for an individual to be 25 years or older and using cannabis in whatever form occasionally or maybe even frequently than it is for a young person aged 14 to 25 to be using cannabis either by smoking or vaping or by edible or any other form on the brain and body it's absolutely clear that the brain continues to develop at least until age 25 and that a huge number of systems related to mood regulation so-called executive function the ability to organize one's thoughts plan and execute plans essentially to become a functional human being right that's one portion of becoming a functional human being but certainly an essential one all of that relies on the fine-tuning of this neural circuitry that we've been talking about up until now and it's abundantly clear that cannabis and THC in particular dramatically disrupt those processes so if this isn't clear enough just from my statements I'd like to point to a particular paper this is one of the more impactful papers in this area in recent years this is a paper published in Lancet psychiatry in 2022 title is Association of cannabis potency with mental ill health and addiction a systematic review there are a number of very important points in this very fine paper lens at Psychiatry is one of the Premier Medical journals out there and they eval valuated a huge number of studies they actually looked at more than 4,000 studies they selected the ones that were only the most rigorous in terms of study design and Analysis and rigor of conclusions and they looked at how early use of cannabis impacted later probability of development of psychosis and other psychiatric conditions and the takeways from this study are very clear first of all chronic cannabis use so more than twice per week has consistently been associated with mental health disorders I'm pulling some phrases directly from the paper heavy Canabis use meaning cannabis use more frequent than twice per week has been associated with four times the risk of psychosis later in life in particular schizophrenia and bipolar likee episodes now we've done an episode on bipolar disorder so-called bipolar depression we have not yet done one on schizophrenia but both bipolar disorder and schizophrenia have a very very strong genetic component there's a 3030 30 times greater likelihood that you'll have bipolar disorder if you have a first relative who has bipolar disorder and then it's also the case that using cannabis especially during adolescence and the teen years and up until age 25 create a four times greater risk of psychosis for those that have a predisposition to bipolar disorder Andor schizophrenia now I don't hear very much about this in the media this paper got some attention and then it sort of uh got swept away I don't think there was an intentional sweeping away there's just a lot of events in the world as you uh well know but I think it's a particularly important set of findings because obviously it in looking at so many studies it distills out the strongest findings that are out there and really pulls the the the consistent messages that are arriving from all these different studies and as they point out and again I'm paraphrasing here this is the first systematic review of The Association of canab potency and all of the data point to a very clear conclusion which is the more potent the THC concentration the higher probability of developing psychosis or a major depressive episode or a major anxiety disorder later in life that should be of particular concern because we know we are absolutely clear about the fact that with the Advent of all these new strains of cannabis and with the engineering and availability of cannabis at much higher potency meaning THC potency the risk of psychosis is going up and up and is likely to continue going up unless something is done to reduce the frequency of cannabis use to zero ideally or to very low frequency very low potency in adolescence and teens and people age 25 or younger I know a lot of people don't want to hear this message because first of all it's alarming and second of all as I mentioned earlier the statistics tell us that the greatest number of people that are starting to use cannabis are in the age bracket of 16 to 24 many of them are functional in other areas of life they are students they are employed Etc but when you couple that with the fact that the most frequent adopters of cannabis use are in this age bracket of 16 to 24 they're twice as likely to use as other individuals or to start using cannabis as our other individuals plus the general perception out there because of the way that cannabis is discussed in the media and by sports figures and by celebrities and by by politicians Etc that it's not as bad as alcohol and maybe not that bad and maybe even has health benefits then you're essentially setting up a system where young people are far more likely to adopt and continue cannabis use without realizing these serious health consequences that await them later with all of that said I of course again want to acknowledge that there have been well demonstrated effects of cannabis for reducing pain in particular in chemotherapy and in the context of reducing nausea in people suffering from cancer or chemotherapy there is a well-known effect that one can generally point to as positive using cannabis for things like glaucoma for lowering intraocular pressure and offsetting the loss of neurons that would lead to blindness although there are other tools of course that don't involve cannabis use that can accomplish that as well so-called intraocular pressure lowering drugs or drops there is a list of probably a dozen or more psychological and bodily ailments that can be aided by cannabis use in particular edible cannabis use of particular strains of course am going to address each and every one of those in episodes where I'm talking for instance about eye disease about chronic pain I am in no way shape or form trying to rob the incredible efforts of the Laboratories and people that have worked very hard to study and establish the valid uses of cannabis for treating various ailments and that continue to study cannabis in order to try and amarate the symptoms of different ailments but today I really wanted to emphasize the biology of cannabis some of the often discussed effects I guess one could call them postive effects things like enhance creativity and really point to the nuance and actually the Divergence of people who take cannabis and some experience heighten levels of creativity and some do not some people experience heighten levels of sexual arousal and some people experience the exact opposite and so on and so forth rather than focus on all the potential positive and sort of emerging positive data about cannabis in different medical contexts and at the same time I strongly feel that it's important to acknowledge the shocking because there's really no other way to describe it the shocking effects of cannabis use on the developing fetus and the fact that so many pregnant and lactating mothers are using cannabis I mean that number 15% still has me you know dizzy with kind of disbelief and yet we need to acknowledge this and address this immediately and I think it's vital to understand that cannabis use through any delivery mechanism smoking or vaping or edible or otherwise is very very concerning in fact dangerous to the developing brain certainly for the fetal brain and for the baby brain but also for the Adolescent brain and for the teen and young adult brain not just because of the effects that it can have in the immediate term those slow creeping increases in anxiety and depression brought on by cannabis use but also the time release if you will on the development of psychosis and other types of major psychiatric disorders later in life I acknowledge we've covered a lot of ground today and yet there's still far more ground that we could have covered and that we will indeed cover in future episodes nevertheless if you are learning from and 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