Welcome to Better Brain Fitness, hosted by doctors Josh Turknet and Tommy Wood. In this podcast, we will explore the frontiers of how to keep our brain fit and healthy so that we can perform at our best and do the things we love for as long as possible. Let’s go. All right welcome again to another episode of the Better Brain Fitness podcast. I am joined today by my sensational cohost, doctor tommy Wood hello, Tommy hello someday, someday I’m going to have to do the intro so I can say those things about you that I like it this way.
00:43 : Today’s we have a question that has been submitted by a few folks. One of them came in by audio and was left by Mark, who I think is in California. So I will play Mark’s question now. Hi, my name is Mark Neal. I’m a long time brain Joe subscriber and fan. And I have a question based on the last podcast where you spoke about alcohol. I’m curious about what the current research is about the effects on the brain of cannabis use. And specifically I’m interested in long term use and what the effects are for those of us who perhaps used cannabis in our younger years but have since stopped for a considerable amount of time.
01:37 : Anyway, I love your show and what a, what a great voice of reason you bring to questions about the brain and brain health. Thank you very much. All right, Well, thank you so much, Mark, for that question and for your kind remarks so I’ll do my best to give kind of an overview of the effects of cannabis on the brain, particularly long term so briefly, you know how cannabis works or marijuana so the main psychoactive ingredient in marijuana is THC. So that’s the compound that’s kind of responsible for the high and the neurological effects that people experience.
02:19 : And THC binds to two different kinds of endocannabinoid receptors, CV1 and CV2 and the CV1 is the one that’s most prevalent in the nervous system there are other receptors throughout the body and different tissues. And when it binds to those brain receptors, it disrupts the kind of the normal function of that endocannabinoid system. And that’s what’s responsible for the effects that are experienced, you know, acutely after it’s inhaled or ingested. And it also leads to the release of dopamine in the brain, which is thought to be, you know, behind the characteristic euphoria or high that people experience.
03:02 : But then the other effects of THC on the brain depend on kind of the regions where those receptors are primarily expressed and concentrated so one area is in the hippocampus and so This is why, you know, disruption of those circuits there can impair memory formation and consolidation of memories. It’s also expressed highly in the prefrontal cortex so we see it impacting things like attention and impulse control and then also there are high concentrations in the basal ganglion cerebellum, which are two areas that are deeply involved with movement so you see impairments and coordination and balance and of course those effects, you know, are going to vary depending on dose and individual sensitivities as well as a specific, you know, strain of marijuana product.
03:50 : So obviously, just like alcohol, it impairs cognition when it’s in the system, though there has been sort of a belief that it may enhance creativity. It was kind of an amusing study that was recently published showing that it seemed to make people think they’re more creative, but it didn’t necessarily make them objectively more so. And then but the larger question, and I think the one that Marks has here and that the others have asked as well, is it what are the longterm effects or are there any longterm effects, particularly, you know, longterm downsides? So for one, unlike alcohol, cannabis is not a neurotoxin. So, you know, at high enough amounts, alcohol is unequivocally very bad for the brain.
04:32 : It leads to the death of neurons. And with cannabis, the question of longterm effects is a lot more difficult, especially when we’re talking about kind of more occasional or recreational use and it seems to be for multiple reasons. So for one, if it’s long term consequences are less pronounced, then they’re going to be harder to detect it’s going to take more, you know, more people to study to tease those out. We can’t do the kinds of studies we’d really like to do to determine these effects in humans, like a randomized controlled trial over many years.
05:03 : And the studies that we can do, the data we can look at are these observational population studies, which for one can only give us correlations. And those correlations in this instance are likely confounded in many different ways. One of those is that cannabis, you know, has been illegal for a long time and many places still is. So it’s someone who is using in that is more likely to be, you know, using other drugs as well that have more clear evidence of harm and also look more likely to be engaging in other, you know, unhealthy or risky behaviors that may impact their health and including brain health.
05:39 : So what we kind of have to do is do the best we can by kind of triangulating the limited, limited information we have. And one place we can look at to kind of get a sense of possible areas of concern are animal studies where you can kind of conduct more controlled experiments. And it has been shown in animals that disrupting those endocannabinoid signaling pathways impacts synaptic plasticity. And that seems to be particularly problematic during adolescence. And you know that disruption is of synaptic plasticity is, you know, the main consequences that would be for learning and memory so, you know, changing the OR adjusting the weights of synapses is how we form new neural networks that allow us to learn new knowledge and skills to retain memories.
06:30 : And that process relies on very precise timing between neurons, and that precision has been shown to be disrupted when THC is activating those CB1 receptors. So that’s thought to be the mechanism by which it’s ultimately degrading the quality of those networks and cognitive function, especially in adolescent animals. And then both of the structural and functional changes in those brain circuits that happened during adolescent exposure have been shown to persist into adulthood in the in the animal studies. Now it’s important to know that doesn’t mean they couldn’t be reversed by some kind of intermention, but that’s not being done in these in these research.
07:13 : But it does mean that in this case at least those the changes are lasting in the absence of anything to try to reverse them. This podcast is brought to you by the Brain Joe Academy. The Brain Joe Academy provides brain boosting whole brain stimulation in the form of neuroscience based musical instruction designed for adult brains and with no prior musical experience required. Start your brain boosting musical journey today at Brain Joe dot Academy.
07:48 : So that’s kind of the animal models showing impacts on synaptic plasticity. The human data is mixed and murky, as you’d likely guess, again because it’s so difficult to study, and there’s also been comparatively less research in this area because it’s been an illegal drug for so long so only more recently has it been researched a lot more heavily. So first question, you know what are the kind of the functional consequences of long term use? One 2020 meta analysis that looked at adults who had near daily use for over 2 years found what they referred to as global decline in neurocognition.
08:31 : It was about a quarter of a standard deviation worse than that of non users. There was a longitudinal study of a little over 3000 people aged 18 to 30 who were followed over several decades and including a cognitive assessment that was done 25 years after the initial study was launched And that one showed that the cumulative years of exposure to marijuana was associated with worse verbal memory.
09:00 : And then a couple of longitudinal twin studies that showed that there was a decline and vocabulary and general knowledge with being a cannabis user, but interestingly not with the amount of cannabis consumed. So those are sort of the functional consequences that have been identified. And then structurally we can look at kind of are there any sort of changes that occur in the brain kind of at the gross anatomical level using imaging.
09:29 : And so there was a longitudinal study using Mri’s. This was done in adolescence at baseline and it had a five year follow up. And there was shown to be a dose dependent association between cannabis use and thinning of the prefrontal cortex, which again is one of the areas where there’s higher concentration of the receptors. And then there’s another meta analysis found that regular cannabis consumption was associated with smaller hippocampal size as well as smaller medial overfrontal cortex relative to non users.
10:04 : Then there’ve been other large studies that haven’t shown the same kind of effects so there was a twin study that was done, or two twin studies, actually one from the US1 from Australia, which showed no differences in the volumes of a variety of different brain regions. There’s also some evidence to suggest that longterm use may impact executive function or cognitive control. So cognitive control is really about frontal lobe being able to sort of coordinate the activity of all the other brain regions. And it does this mainly by suppressing or inhibiting activity in other brain areas that it, you know, doesn’t want to be active or contributing. So it’s basically kind of your ability to pay attention to the right things or the things that are kind of in line with your goals at a given moment and to also to recruit the relevant parts of the brain to that particular task.
10:59 : So for example, if I’m studying for a test and a coffee shop, I need to tune out the conversations of people around me, and I also want to be turning on the parts of my brain that are relevant for processing the information that I’m studying and that ability of your frontal lobe to suppress or inhibit. You know that extra activity that you don’t want may be compromised with long term use. And there is an EEG study that revealed findings and long term users that would kind of support that effect of limiting the frontal lobe’s ability to suppress sort of extraneous brain activity.
11:32 : And then as we know there’s there are now sort of medicinal uses for marijuana. One is chronic pain. It’s also used in people in multiple sclerosis. There been studies in those populations where, at least in the doses used for chronic pain, there were no significant neurocognitive differences noted in subjects and same was true of the compound that’s used in Ms oral droneabinol. No differences there in MRI measures, so including changes in brain volume. So that’s kind of you know overall the main findings in terms of humans with respect to brain function and correlates of brain health.
12:16 : There’s also some concern about a heightened risk of stroke there have been some studies that describe an association between cannabis use and increased risk of stroke and it does seem to be that correlates with you know the that’s dose related in other words, you know, the heavier use, more frequent use, it may increase the risk of stroke. That issue is confounded significantly by the fact that cigarette smoking is also common in people who use cannabis. And I don’t think there’s anything that’s really been able to tease that out to determine if, you know, if there’s a distinct increase risk from cannabis and isolation but there’s enough of a signal there for there to be some concern about that issue.
12:55 : So to kind of summarize what I take away as sort of where things stand right now and remembering that this isn’t medical advice but kind of what I would say do a family member asking this question so I think it’s likely that heavy regular use and I think most of the studies or some of the studies at least we put that at four times a week or more does have long term effects at least functionally speaking on memory and learning and possibly as well on cognitive control or executive function.
13:29 : So you know something to take into consideration if those are things that you value. I think it’s also worth to factoring in the timing of it if you are learning new things or doing things that are cognitively challenging so for example, if you spend a couple of hours studying really hard or working on a new skill, it’s probably not a good time to, you know, have some right after that.
13:51 : Or, you know, even the same day probably better, save for times when you’re having kind of a the chill day of taking it easy and not doing anything sort of cognitively challenging. And they’re also are likely, you know, significant individual differences in the impact of these things. You know, functionally, structurally, maybe, you know, may vary a good bit from one person to another. I think it’s wise at this point in time to say, avoid it during adolescence and certainly during pregnancy it’s known to have issues if a developing fetuses is exposed during pregnancy and occasional use otherwise doesn’t seem to be clearly associated with any issues, I would say also, if you are noticing issues with memory or learning when you aren’t, you know, actively using or when it’s not in your system, then I think it would be wise to stop until we know more.
14:41 : And I’d also say that headtohead cannabis is almost certainly less harmful to the brain than alcohol at kind of all levels of usage. So if you’re picking a poison, it’s probably the lesser poison. And the last point to make here, one of the big limitations of these population based studies is we can’t look at individual variations. We can only see these average or net effects or these effects on a population as a whole can’t tease out cause and effect, and you can’t tell differing effects of context you know whether something that maybe is harmful in one situation is helpful in another, or even harmful in one individual and helpful in another.
15:24 : So in other words, there could be scenarios where the benefits outweigh the harms in a particular person or in certain circumstances. You know, obvious example being cannabis has some medicinal uses and the reason it’s approved for those is it’s thought to be better to be taking it, you know, for someone’s help than not taking it so there’s thought to be a net benefit. Another example, if you’re a type A personality and you occasionally use it to reduce stress and it’s mitigating all those damaging, all the damaging impact of cortisol on tissues throughout the body, that also could be beneficial so there are, you know, many potential scenarios where this could be true, and we really just don’t have the tools to answer those kinds of questions in a research setting.
16:12 : Same is true to some extent with alcohol, though you know likely fewer circumstances but you know one example, a person with social anxiety who just drinks at a party or the social function and you know, is able to form a relationship or a friendship with someone who they wouldn’t otherwise have talked to that could be profoundly beneficial for the long term help and that you know something that made possible by having a drink.
16:37 : So and I think it gets back to the fact, you know, the conversations around these particular issues are not ultimately about hard and fast universal rules, but rather giving people all of the known science to make as informed a decision as possible for their own circumstances. So again, I’m sure we’ll learn more about this particular topic, cannabis and the brain over time and we’ll update you guys as if our opinions change on it. Tommy, anything you have to add there? Yeah, a few things sort of come to mind.
17:14 : Just to kind of based on some of the things that you said and I’ll try and remember everything I thought of as a cannabis user as an adolescent might have held, held me back a little bit. But I guess one of the first things is you mentioned the risk of stroke and obviously you say that cannabis users are more likely to smoke, but it also depends on how you what your delivery vehicle for the cannabis is in the 1st place. So you know, often it is as part of a tobacco based split if you put some hash or some marijuana leaves into that. So then it’s confounded by the fact that you are technically smoking a cigarette at the same time and often without without a filter.
18:04 : So you’re getting more of the bad stuff and then you know as part of that there’s a whole bunch of things that come along for the ride that we just don’t know very much about and this isn’t, this is just acknowledging that we don’t know one way or the other so there are a bunch of different cannabinoids. There are also a bunch of terpenes and other compounds that they may be having some effect they’re just understudy that we’ve mainly focused on THC and then CBD which i will mention as well so I think some of the you know, associated downsides of long term cannabis use could be due to the delivery mechanism rather than you know THC itself.
18:48 : And CBD or cannabidiol is interesting because generally when THC is used pharmaceutically they come as a combination and CBD has slightly different effects it doesn’t necessarily directly bind to these CB receptors, but what it does is it seems to upregulate or augment the signaling of endogenously produced cannabinoids so there’s this whole system called the endocannabinoid system, which is, you know, part of our normal Physiology and neurotransmission where we make cannabinoids that bind to these receptors that’s why those receptors are in the brain in the 1st place, things like anandamide. And so CBD up regulates anandamide or augments or anandamide signaling and these things are also are beneficial in the gut so there’s some interesting data in mice in models of inflammatory bowel disease where CBD augments and my signaling in the gut and this actually decreases inflammation in the gut and i know some people who feel they’ve received benefit from specifically CBD which is non psychoactive but having some improving some of their gut related symptoms and then, you know, the gut and the brain are connected, you know, maybe there’s some potential benefit there as well.
20:05 : Directly CBD is actively being investigated as a neuroprotective agent so I’ve even tested CBD in my lab in a in a rap model of this was neonatal brain injury but it’s also being tested in traumatic brain injury and stroke and a number of people who are working in that arena And there’s some interesting data although it’s not you know it’s not a conclusive yet which is why it’s this doesn’t have an indication in humans because some studies show benefit and others don’t but it but it’s interesting and again there may be a bunch of related compounds that could be doing something similar and I think there’s going to be a lot more research into the various cannabinoids and there and their effects related to that is the fact that in individuals who have some kind of pain or trauma so veterans would be a population where this has been studied they often use cannabis to self medicate some of their symptoms and that could be related to anxiety or problems with sleep or chronic pain.
21:06 : And it’s you know very subjective and self reported but if people are seeing benefit, you know, even if it’s a subjective benefit, that’s probably going to going to sort of may improve things over time because they’re less anxious or stressed. And you know, I think that’s something that again, we don’t know enough about, but it’s just interesting to see that this is happening and people are reporting benefit. They often go into these, you know, specific strains you mentioned the strains and people often have a favorite strain. But what’s interesting is that when they’ve looked at strains, they don’t routinely or you know, have the same proportion of the different compounds so people like well I like this strain because it makes me feel this way.
21:53 : But then if you know go and analyze those strains depending on where that strain comes from or was grown, you know their the compounds in them are all over the map. So it’s interesting that some sometimes people think well this strain has more of this and if we get more of this effect but that’s unlikely to be the case, that’s probably placebo, placebo effect right. And so then I guess the final thing related to the initial question particularly, you know somebody used this previously in life even as an adolescent and then you know, maybe have not used it for a long period of time or you know, very irregularly.
22:33 : You know, I kind of feel like a Stoic philosophy is good one to take care you know whatever happened has happened and you know, it’s probably going to be worse for you to worry about what you’d previously done, you know and the stress associated with that because there’s nothing you can do to change that so even if there was some harm from, you know, very extended or you know, high dose usage at some period of time in your life, you know, hopefully that’s water under the bridge now and we know that as the brain remains plastic pretty much throughout the entire life.
23:09 : Other things you can do to improve your cognitive function around, you know, physical activity, sleep that reminds me, I was going to say something about sleep, physical activity, sleep by other forms of cognitive stimulus we know that you can change your trajectory of cognitive function at any time in your life, essentially, except for in the, you know, the later stages of dementia. So whatever happened previously, you still have control over your cognitive function, you know, by instituting all the stuff that we’ve been talking about.
23:39 : So I just, I wouldn’t worry about it. Just like I don’t worry about it. Whatever happened and I was having a good time with friends so probably some benefit like you said there Josh. So the final thing I was going to say about sleep is that specifically in those populations, multiple sclerosis patients, people with neuropathic pain, there may be some benefit in terms of improving sleep and that might may be one of the reasons why you know this sort of this there’s this balance you know, potentially some of these compounds may affect the brain, but if they’re at the same time they’re supporting improved sleep, those things could, you know, balance out and that certainly seems to be the case, is no net detriment, at least when it’s been studied in those populations.
24:22 : Higher doses of CBD on their own seem to be stimulating. So if you just take a lot of CBD right before bed, it may negatively affect your ability to sleep. Other people report smaller doses you know, in the sort of the few milligrams, you know 5 to 10 milligrams of CBD improves their sleep. But you know in studies where they’ve looked at maybe 100 milligrams or 200 milligrams that seems to is seems to be stimulating and can negatively affect sleep.
24:51 : Where the cannabonols have been you know suggested to improve sleep is in the setting of a combination of THC and CBD and generally in a somewhere between a one to one to three to one ratio of THC to CBD and again then you’re only talking a few milligrams but that’s specifically in those populations where you know this is being with this is approved as some kind of medication so multiple sclerosis or something like that then there may be may be some benefit to sleep.
25:26 : So like you say it’s kind of a big messy bunch of research. But you know there are some indications where you know certain cannabinoids may be beneficial to the brain but we’re still, I’m picking a lot of that and hopefully a lot more to come in that arena. Yeah and as you said back to the original question in terms of longterm issues, a you know, there’s not you could, it’s not going to change what you do, right but be there isn’t any evidence that we have that there are any kind of irreversible pathological effects that are happening and like as you mentioned, the fact that the brain remains plastic, you know, is reason to believe that whatever effects there are could very well be, you know, reversed or mitigated by that.
26:14 : Another important thing that’s notable is that the studies that are done are heavily biased towards looking for negative consequences and that’s a limitation, something that may have, you know, some real positive benefits so there is kind of a negativity bias in the literature. There were studies showing that occasional use, they were parts of the brain that had increased size of Gray matter, if that would be, you know, potentially a positive sign and that it may change depending on the chronicity of use. And then the last thing I was going to say is that people get really confused with cannabis and all the different compounds and t h c and c b d.
26:56 : So what I’m referring to in the in my discussion is specifically THC which as we said is the psychoactive component. Cbd is also part of cannabis and you know isolated and taken, it does not appear to have any negative impact on the brain and in fact may have multiple benefits as Tommy described so keeping those kind of two things distinct is challenging but important. All right well, thank you guys for the questions that keep us on our toes and this will likely be an evolving topic. If you have anything, any questions that arose as we were discussing this or anything else in the realm of brain health and fitness that you want us to tackle, you can give it to us at brainjo.academy/questions. Okay that’s all we’ve got for this episode.