#36. Drugs 101: Cannabis - Professor. Tim Karl

Professor Tim Karl of Western Sydney University. He joined to give us a basic overview into the world of cannabinoids. He spoke about what happens in our brain when we use/abuse cannabis and all the different components the plant has. This podcast covers where research is in terms of the benefits of medical marijuana, some of the concerns which people need to be aware of and how the media often misrepresents findings in this space.

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Transcript

uh all right welcome everybody to the smooth brain Society I am Sahir um and today with us we have Dr Tim Karl he

is he is a professor at Western Sydney University where he continues his pre-clinical research into schizophrenia and Alzheimer's disease although the real reason he is here today is because he investigates the detrimental and potentially beneficial properties of cannabis um and the use of cannabis uh in treatment or um in its effect on brain disorders uh so welcome Professor car to the podcast thank you very much for having

me and as always we have a co-host uh today our co-host is Terise Broodryk she was on last time as a as a guest herself talking about the politics in New Zealand but now we've she's been gracious enough to flip that around and now be a guest in uh so be a co-host to someone who is now on the neurology side of things so moving away from social psychology this would be interesting so yeah welcome TR thank you um I'll oh no you go you go yeah I was just Gonna say I'll let you get started okay cool you have a question um so as a social psychologist um if we could bring it to basics for me for understanding uh how does cannabis affect or impact the brain so cannabis um impacts the brain in a way because there is already endocannabinoid system available in the brain so that means we have have already a setup in the brain with receptors and neurotransmitters and enzymes which processes neurotransmitters which are very similar to what happens when you use cannabis so if you smoke cannabis the cannabinoids within the plant activate this system in the brain and then produce certain behavioral effects which people are aware of of when they consume cannabis in one way or the other the two main receptors which are related to this system are the cannabinoid receptor one and two where the cannabinoid receptor one is the one which gives you the the particular High people feel when they use recreational Cannabis but it also drives a lot of the other effects in terms of anxiety in terms of cognition so learning and memory um in terms of sedation uh some of the effects of cannabis which are now to affect paint perception for example are also driven by this receptor so it is basically a a plant material which has components in the plant there can be up to 100 different cannabinoids that's sometimes for people hard to understand it's a very complex plant so a lot of people talk about THC Delta-9-tetrahydrocannabinol and they also talk about CBD cannabidiol but there at least another 70 80 80 or 90 other cannabinoids in the cannabis plant and they access the system in the brain and therefore have effects on your behavior um and potentially because that is obviously what I research also your risk to develop certain

diseases cool um is there a reason that we already have a cannabinoid system in the brain would is there one for why we already have this so it takes it has obviously quite a few um import so so perhaps so the reason is obviously that certain processes in the brain has to be driven by by systems and by neurotransmitters which are available uh and the cannabinoid system has been evolutionary established um quite a while ago so you also find it in in lots of different animal species um so it's highly conserved and it's also the CB one receptor for example is highly expressed in the brain so you find it in nearly all areas of the brain um the reason why we have this system is that obviously certain behaviors certain physiological responses of your body have to be controlled by one system or another and the endocannabinoid system is available to address or to trigger and mediate certain Behavior responses it also for example has a quite uh important role within the immune system this is why we for example look at the cannabinoids as a therapeutic option because in a lot of diseases you have an increased level of inflammation in the brain and the cannabinoid system is able to combat or reduce this inflammation in the brain and these are some of the roles the system has taken on and evolutionary I can't tell you why it was done via the endocannabinoid system and not another one but evolutionary it has evolved to be the m one of the main systems which you can Target to achieve some of the therapeutic effects we are interested in the context of the research we are doing in my

lab nice um a few a few other questions come to mind the first one is well still on the I guess on The evolutionary side of things um do does our body produce something naturally which activates these systems is that why we have them or are there other things apart from because when we think of cannabis we just think of you know the plant and smoking it and so on um so do how are these activated naturally per se without yeah use of any external drugs yes so there are two and we call them endocannabinoids compared to the external cannabinoids which you for example would get from the cannabis plant um so there are two endocannabinoids already in our brain the one is 2-AG and the other one is AEG or anandamide and those two are produced and help with moderating some of the symptoms or some of the behavioral effects for example I alerted to and these are ingrained into the brain they are produced by the brain The receptors are set up for these endocannabinoids so CB1 CB2 are basically have evolved to be able to communicate with this neurotransmitters however because we can access external cannabis you can also obviously activate them by abusing cannabis and therefore yes there's an endogenous system available which works on itself but people who abuse cannabis are then activating this basically from the outside to trigger trigger similar effects as you would find in the brain

anyway cool um no I that's pretty interesting to know uh because yeah it I guess not dispels the notion but at least common knowledge is probably not that um so the cannabinoid system you said it affects a lot of uh functions in the brain ums a lot of regions uh could you probably give us an insight into one or two of them as to how they probably work maybe one's more relevant to your research but you mean in terms of H how the um cannabinoids impact on the release of other neurotransmitters or are you rather behind the behavioral effects they are

inducing um maybe we could start with the neurotransmitters first what do you think there is and then we can talk about behaviors after so when when cannabinoids are used it affects and I have to clarify yeah I'm not a cannabinoid researcher so I look at the effects of cannabinoids on Behavioral Systems and on brain disorders so if if you want to delve into the the details of what cannabinoids are specifically done on for example a neuron level you probably should talk to a cannabinoid pharmacologist um because that's really outside my area but strictly speaking the cannabinoids are endocannabinoids or external cannabinoid like the phyto-cannabinoids they target the endocannabinoid systems thats the CB1 or CB2 receptors for example um and the um cannabinoid receptors a g protein coupled receptor receptors and they can activate or inhibit a number of Eternal signal transduction Pathways um I can dwell into this more I'm not sure how how easily understandable that is for the for your audience so it inhibits for example calcium channels and sodium channels at the neuron level um it also inhibits ATI potassium channels um activates potassium channels which are INB rectifying and those effects for example result in the could result in changes in the dopamine level on the brain level and that can lead to Euphoria amongst other effects so that would be on a on a neuron level what cannabinoids are actually doing by opening and closing certain channels resulting in the release of other neurotransmitters which then induce behavioral effects in the patient or in in people who recreationally use

cannabis that's probably quite theoretical that was very

theoretical uh yeah so let's talk about the Behavior then that's

better uh yeah so there there are different cannabinoid have quite a few effects so um the the main affects people and and I stay away at the moment from what might be therapeutically um relevant for cannabis consumption the main ones people talk about when you just think back in the days about the recreational use people might experience the high if the if the dose is is um sufficient enough um people might dependent on the do and that's where where it starts already to be quite complex if you have um used a high dose GC cannabis strain for example you would you might experience increased anxiety if you use low dose um THC cannabis strains you might have a reduction in anxiety if you have um abused cannabis for a long time it might actually impact on your ability to uh perform well in cognitive tests so it might impair to degree your learning and memory um however nowadays cannabinoids are also looked at in regards to improving cognition in Alzheimer so again it depends very much on what strain of cannabis you might be abusing or you might have access to cannabinoids can reduce um body temperature if you use very high dose um THC it reduces so we call it a sedative like effect so um it would inhibit your your interest to move around so as um you alerted to I do preclinical research so we if we use high dose THC in rodents they for example don't move as much anymore so they are slightly sedated um but then coming into the therapeutic Arena can have been shown for example to have anti-convulsant effects so that's why that the moment looked at or have to a degree at least already been established as a effective treatment for epilepsy or certain types of epilepsy um it can also have effects on your social abilities so if again if you use high dose or THC um and which strains it might might reduce your drive to socially interact with other people and might actually result in something which is called social withdrawal uh which is relevant for schizophrenia that's why cannabis abuse at least at certain times of your development is seen as a risk factor for developing schizophrenia so these are some of the behavioral effects people are aware of when they talk about cannabis AB so you have the high it has an impact on anxiety but it really depends on the dose it can have an impact on your cognitive abilities um it can be sedative again all dose dependent but it also might have some Ben beneficial effects including being an

anti-convulsant um did I hear you correctly in saying that um while typically the idea is that uh cannabis will reduce cognitive um functioning or impact cognitive functioning in a negative way that for Alzheimer's um patients it might improve um cognitive or did I hear you mis hear what you said no that is correct and that's where the where the complexity that that's where the complexity comes in um and it really also depends a little bit on who you would talk to so I said I'm not a cannabis researcher per se I use preclinical research models to understand risk factors of uh certain brain disorders and to also look at potential Therapeutics so when I go to cannabis Focus or cannabinoid research Focus conference a lot of times the focus is on some of the positive effects of cannabinoids and that can include that and I'm not talking about THC here that is very important I talk about Cannabidiol CBD my own research but that's followed up by others and others have done this now also to a degree at least in clinical trials when you look at Cannabidiol CBD CBD in a mouse model for Alzheimer's where you know that mice over a peri period of time develop cognitive deficits if you treat these animals with CBD they do better in cognitive task after they have received this treatment over a period of time so in that regard it improves the the cognition of these animals or to be more accurate it reduces the cognitive decline of these animals however if I use a mouse model which isn't affected by Alzheimer so there are no normal healthy mice and you would expose them chronically so over a period of time to high dose THC so Delta-9-tetrahydrocannabinol and you test the animals at the end for their cognitive performance so how good can they learn how good can they memorize these animals depend on the dose depending on how long you have um exposed them to THC for these animals might show actually reduce cognitive abilities so they will take longer to learn they might not memorize as much to learn and then to make it even more complex there's one study from Germany which was published I think five or six years ago where they tested in aging mice so the animals were not Alzheimer's mice or had a genetic modification which would make them close to an Alzheimer's related model system but so these animals were just aging mice they were around 2 years old and they exposed them to low dose THC and at the low dose at this Advanced age it actually reduced the the Aging related cognitive decline of these animals so depending on who you ask and depending on what they are talking about people will tell you cannabinoids in potentially have ability to improve cognition but in all likelihood that's not linked to the effects of THC if people talk about that cannabinoids or cannabis impairs your cognitive effects or your cognitive ability saying all like you talk about high dose THC so it really depends on who you're talking to and what type of studies and what type of cannabis exposure they're referring to it gets even more complex so if you use if you look at these animals which have initially been treated with high dose THC at a young age and then you test them their for their cognitive behaviors and they do worse because they had high dose THC for an extended period of time if you test them let's say two months later again but they don't have any THC exposure during this time they might might actually have come back to the normal levels of animals which never had seen cannabis in their life so it's not necessary a chronic effect on the cognition but it's a relatively short term effect that if you if you abuse cannabis or if you have recently abused cannabis talking about the mice here that these animals then show an impairment in in cognition so yes it's basically dependent on what cannabinoid you're talking to you about what what dose you're referring to you can argue both You could argue it actually improves cognition or it might be actually detrimental for your cognitive performance and this this is why you find all sorts of media announcements regarding what cannabis is doing because people quite often don't consider that it is a complex plant that people when they use it recreationally in all likelihood it's for example very high in THC because that gives you your high but that might have a detrimental effect on your cognition whereas when people talk about cannabis potentially being used as an Alzheimer's treatment they normally talk about cannabis which is is very low in THC but very high in CBD but if you buy cannabis on the recreational Market or the illegal Market it's in all like you high in THC and low in CBD so it's really dependent on what what you are talking about and what you're looking at in in

particular oh that was really good I think I think that part needs to be clipped out and played again and again like you need to remember there's a difference between THC and CBD and when people are talking about these things in research you need they're very specific about it but the media doesn't and uh and then can cause issues in terms of result interpretation yeah I can give you one example the first study we published on Alzheimer's disease transgenic mice or animals which are genetically modified that they develop a kind of behavior and a kind of brain um pathology which is relevant to Alzheimer the animals not have really Alzheimer's disease but they have certain aspects of Alzheimer's disease and therefore we can test them we exposed them to purified Cannabidiol CBD so now cannabis there was no THC involved it was a purified compound just Cannabidiol we published that in a medical journal and just stated that if you expose animals to purified CBD they do better in behavioral tests afterwards which test for learning and memory the first news Outlet which covered the story that cannabis is treating Alzheimer's disease which was very far removed from what we actually had done we hadn't used cannabis we hadn't even used THC we hadn't used any of the other 100 cannabinoids but obviously it was a way better story to say cannabis treats Alzheimer's disease and after after that I got lots of people who wrote to me and said listen so can I get somewhere and that was before cannabis became or medicinal cannabis became legal or at least accessible to people in Australia I lots of people who ask me if they now can use the um recreationally used cannabis to help their relatives who are affected by Alzheimer's and and I had to explain that what we had done is very very different to an approach where you use some sort of cannabis strain you don't know the cannabinoid content and and the the mix of cannabinoids in this plant and this just think then that this might be a a therapeutically effective way to help um relatives or or your family members um but yeah media obviously picks up on whatever sells the best

story uh I wanted to ask uh this this kind of comes back to this reminds me of my PhD exam when you ask me this question in relation to alcohol but when we're talking about dosage uh and you're talking about High Low Dose how how well does it translate between mice doses for cannabis for and human doses for taking high THC low THC High CBD low CBD how how well does it translate what are we talking about in terms of yeah numbers so there is a in in Pharmacology there is a certain formula where you can try based on the body surface and the body volume to work out what it dose in a human might translate to in a m in a mouse the other way to do is is obviously if if you know the for example behavioral effects of a certain compound you can just try to dose it in a way that you achieve the the same effects in your mice which you would see in humans or the other way around so when we talk about cannabinoids in terms of the purified cannabinoids so working on CBD or working on THC we are able to relatively well model what you see in humans and in animals and compare it the the so a high dose um in our mice for example high dose THC would be 10 miiligrams per kilogram body weight in an animal so that would be a high dose THC in mice if you inject them with this high dose it probably would increase their anxiety they would say show sedative effect so they wouldn't move around a lot um it also in all likely if you give it chronically it would impair their cognitive performance a low dose  THC approach in mice would be something lower than 3 milligrams one other people would probably argue it should go as so as one milligram per kilogram body weight how does it translate into plant material this is very hard to answer because there are so many different cannabis strains out there with so many different ratio of cannabinoids in the cannabis strain that it becomes near impossible to get any comparatively insight from using purified cannabinoids compared to cannabis strains that it's the moment what the um field tries to rectify so in our lab for example we started off just using purified cannabinoids and we work with doses of CBD for example anything between 5 milligrams per kilogram CBD to 100 milligrams per kilogram body white CBD um and now we start looking at cannabis strains which are high in CBD which to a degree has the same ratio so for example at the moment we work with a cannabis strain which when we inject it into the animals they roughly get a mix of 3 milligrams of THC and 80 milligrams of CBD and that would be classified as a CBD Rich cannabis strain be aware that most of the Cannabis which is available and it doesn't matter if this is now because you have a prescription for medicinal cannabis or if you buy it on the on the black market most of these cannabis strains are very high on THC but very low in CBD so what we are using had been specifically designed by a company to be able to look at a can a full cannabis extract and its effects on Alzheimer's compared to purified compounds because obviously in the human world people would be very interested to be able to have access to medical cannabis because it makes it cheaper and they get the potentially positive effects of all the other cannabinoids um which are in the cannabis plant compared to just having one purified

compound um I just wanted to ask in terms of you talk about working with the companies to have the right strains and be able to study specifically what you're wanting to look at how difficult has it been in your experience um doing this kind of research to gain access to um companies and to the ability to work with cannabis under certain governments that might um have prevented this or not wanted this in the past and how's that changed over time in terms of access so it has I I work on cannabinoids now for around 20 years and that's obviously an Australian legislation right um so back in the days and that has that part hasn't changed that much so if if I want to use cannabinoids for research I have to get approval by I work in the state of New South Wales here in Australia I need to get approval from New South Wales Health to be able to access these cannabinoids get them in the lab I have to have a drug book I have to write down how much we use for our experiments that has to be linked to approved animal research protocols uh once they run out the drug approval runs out but it was as long as I stayed within this legal frame worm I had access at least to purified cannabinoids because that's already back in the days companies would have produced them mostly though to look at the detrimental effects however 15 I would say 15 10 to 15 years ago they started obviously opening up the opportunity of having medicinal cannabis and legalizing medicinal cannabis and even though that hadn't been written into legislation yet lots of companies started to pop up so so suddenly nearly every week I got contacted by a new medical cannabis company some of them highly professional others not so much who then said we have these products available do you want to test them for the first few years I I pretty much stayed away from this because I wanted to see how where the field settles and which companies are actually professional and can um last and and basically survive this initial rush and by now you as a researcher you have access to a lot of professional companies who are also able to make sure that the the quality of the cannabis strains you receive is consistent across breeding cycles and across years they check on the cannabinoid content they don't check for 100 different cannabinoids but they would check at the they check for the most 10 or 20 most likely cannabinoids which should be expressed um they might even able to provide some funding because this type of research is obviously um relatively expensive in terms of the legislation around it I still need approval from New South Wales Health if I use products which are uh CBD Focus so cannabidiol Focus this is not an there's a classification system in in Australia the highest classification as far as I'm aware is S8 so back in the days all cannabinoids were S8 nowadays THC which is the psychoactive component of cannabis is still S8 classified so for this I need approvals and I have to have a drug book if I use for example cannabidiol nowadays in my research it's now classified as four which means I still have to notify new south Wales Health that I use it but I don't have to be as strict about the bookkeeping as I was in the past so that has eased up but that's really just I either would record how much I use or I don't in terms of the access I would say purified cannabinoids were always available that hasn't really changed um it has obviously changed for patients but for me as a researcher it hasn't changed I always had access to those but I knowadays have access to a lot of cannabis drains and therefore cannabis extracts which on the one side open up a lot of opportunities on the other side it also makes it harder because you I could test out dozens of different CBD Rich cannabis extracts which all have slightly different compositions of these different cannabinoids and at the moment I think the field struggles to work out what should we focus on so even what is the THC or CBD Rich strain people not necessarily agree on what should be the percentage so a lot of people would say anything which is has a THC content of over 20% is probably a THC rich strain um but then for CBD a lot of people would expect that the CBD content has to be higher than 20% to call it a CBD rich strain um so it makes it more accessible but it also makes it more complex because there are all these different strains out there and different researchers work with different strains and then even if the CBD content is the same the content of the other cannabinoids might not be the same so they might have different effects so we are not all looking at the same um if you want to call it the same medication uh which makes it hard to compare data and to compare

outcomes but yes for me as a researcher hasn't changed that much I have more opportunities I think when you would talk to patients for them it has changed a lot over the last 10 years um they nowadays have at least in Australia they have a a system how they can access cannabinoids they are able to see to degree at least the cannabinoid content of the cannabis extract they are ordering so that definitely I would say has improved because it is more controlled and people understand better what they are using

that's really interesting um I wanted to ask I feel you had mentioned that even when we talk about medical cannabis use medical marijuana um they still have higher contents of THC or they're still THC Rich um is there how has how is that still the case when as far as you've told so far most of the benefits seem to be from CBD and not from THC yeah that's a good question um so I had to look just in preparation for this podcast and there are websites um which are openly accessible um where you can look at what is currently available as medicinal cannabis in Australia and the THC rates go up to 30 40 50% which is very potent cannabis in terms of its ability to induce a high so that comes back to the the you find also other products right you find CBD Rich products but but I looked at Rand.. I think there was a list of 150 compounds and I think I looked at a 100 of those I I would argue that most of those were were still very high in THC so there are two answers to the question the one is although THC induces a high which some people might beneficial as well I will not comment on that but although it induces a high it also has positive effects THC in itself right it for example has been looked at in regards to how it can impact pain um it has been looked at so it has for example also positive impact on if you have inflammation in your brain THC compounds can reduce this inflammation but it says it might come with a high so  I'm not saying that having  the THC in itself doesn't have beneficial effects the issue is it comes with potentially detrimental effects some people might just ignore those and say but I get these beneficial effects and if I also get a little bit higher and if it also might impact on my cognitive functioning I take that as a disadvantage or as a as a side effects as we know other other medications and I'm not talking about cannabinoids the other medication have side effects as well the other aspect to that is that people try to so so there's some research if you just use purified THC and CBD compounds you can if you put them together you can dependent on what you look at and dependent on the ratio of these two compounds you can use them together and if you have high dose CBD it might be able to block or reduce some of the detrimental effects of THC so that means if I have a high dose THC um cannabis train but it still has a certain ratio of CBD in it the CBD and that's at the moment still under investigation right there again you will find research Publications which argue the one way or the other way but you will find studies which show if there's a certain content of CBD in this cannabis strain it will be able to at least reuse some of the detrimental symptoms which you get from THC and as you had mentioned initially for example I I also work and still do work on schizophrenia and in in in uh in the context of schizophrenia using cannabis which is um highly potent for THC is a real issue because that can increase your risk of psychotic relapse it can make the severity of psychosis um can increase that as well but what has been found is that if you give people who have schizophrenia if you expose them to cannabis which is just um rich in THC they always resp respond with more severe symptoms and it's very detrimental if you expose them to cannabis strains which have high CBD load as well these negative effects disappear so you can block them so there is some evidence that THC  so THC uh strains which are uh relatively balanced on THC and CBD might not have many detrimental effects of the THC but you're right that if you look at these databases a lot of those are still very high in THC and very low in CBD in a lot of in a lot of instances the CBD content is less than 1% and this is one of the my from my perspective one of the problems in the field at the moment that people argue a lot about the positives of medicinal cannabis and and  I see in my own research and when I go to conferences and look at other people's research I see there's a definite place for medicinal cannabis because it can have positive effects but if we don't address the issue of THC very clearly also having detrimental effects and try to get the people who access this this type of medication to be aware that they should opt for CBD rich and ideally THC low cannabis extracts you always will have to deal with po potential negative effects by these people using medicinal cannabis and unfortunately when for example you look at the US and you look at Canada where obviously medicinal cannabis has been legalized a few years ahead of time to what in Australia for example has happen happened the number of people who are admitted to withdrawal clinics who mention that cannabis abuse is the main reason why they go to these clinics that number has increased over the last 10 years so you have to be aware that dependent on what medicinal cannabis product you're using you still might be at risk to be exposed to some of the clearly established and I have to be have to say this very strongly here it is clearly established that there are negative effects of abusing cannabis especially if you do it at a very young age especially if you do it when it's a THC potent cannabis strain and this at the moment to a degree is ignored by the field which which is a a real risk because it then induces new problems uh for the future especially if this becomes even more available to

people um uh um so so just talking just talking about uh the importance you said in kind of realizing some of the negative effects as well as uh going back to something you said earlier you did say that you had some research that some effects are not necessarily chronic so once you stop oh well I think you're talking about preclinical mods but once you stop exposure after some time uh your mice tend to return to levels normal to what you would see in a mice which did not in a mouse which did not take uh was not exposed to cannabis or yeah yes it was regards the cognitive performance for example yes that's correct yeah yeah so um is there kind of in that sense is there kind of hope for people who were kind of admitted to these to weh have clinics so who took a lot of use a lot of cannabis too young and then are seeing sort of detrimental effects is there like decent evidence to say that stopping also improves their performance later on or is it more permanent in humans guess so I would I would assume that if you if you chronically as as a human if you chronically abuse cannabinoids or or cannabis and at some St you you stop this then obviously some of the effects will or a lot of the effects obviously will disappear however looking for example at schizophrenia if you and and that has been established um cannabis is not a causal factor for schizophrenia so I would argue that there there's very limited evidence that just by abusing cannabis that you will develop schizophrenia so it's not a causal Factor but a lot of research has been done and I would say very clearly shows that cannabis is what we call a cumulative cause or a component cause for schizophrenia which means that if you abuse cannabis in particular at a young age and what I mean with that is during adolescence teen adolesence teenage years young adulthood and you are exposed to other risk factors for schizophrenia that could be a genetic predisposition let's assume have a family history and quite often what you can hear is when people have a family history of schizophrenia but they are themselves not affected by schizophrenia when they use cannabis they quite often report that they have very strong and to a degree negative unpleasant effects of that abuse and then in a lot of instances these people stay away from abusing cannabis because they real realize it might not be any good for me but coming back to the research it has been shown that if you have for example genetic perios for schizophrenia and you smoke cannabis dur adolescence that you very significantly increase your risk to develop schizophrenia later on if you have gone through that period you have abused cannabis you have Cog genetic position you develop schizophrenia you can't reverse that by then stopping to small cannabis so at that stage it is too late I would also argue that if you because adolescence is still a period where your brain matures and and you know certain synaptic setups are established if you during that time abuse a lot of cannabis that has an impact how your brain develops and how it matures even if you stop later on that at least has initially been set up so the the effects will stay on for long term if you talk about some of the behavior effects of course you know if if you normally experience a high and you experience that you're a little bit withdrawn once you are able to stop abusing cannabis some of these symptoms will also disappear but some of the risks involved with abuse and cannabis to develop a dependence and that might not cannabis is obviously not as much of an addictive drug as cocaine or Heroin for example that all has been established but there is a level of dependency you develop with chronic abuse of cannabis that might be more on a psychological than a physiological level but it's still there otherwise you wouldn't have people going to withdrawal clinics and mentioning themselves that cannabis abuse is the first reason why they actually are coming to these clinics so once this is established it's obviously very hard to get out of this dependent cycle and also the psychology around it so yes certain effects Behavior effects will stop as soon as you stop abusing cannabinoids the risk involved with abusing cannabis early in life can't be combatant with that it's it's too late at that stage um so people have to be very aware of that because I know it is it's quite common that that people start abusing cannabis early in life um I have two two young kids myself I I I wouldn't um how do I say it's my my my way to educate them is to make make them aware that the later you start testing out drugs the better it is because you know there's a critical period for brain maturation and during that time ideally you don't want to be smoking cannabis every day later in life if you know alcohol is a drug as well they might get exposed to to some of these um drugs and they will obviously test them out um but if they can hold hold off with it to to a later period in their life I think that would be a very uh sensible approach to this

that's good that's just spilling up life lessons as well at the same time um more people um yeah I know you have to go soon so maybe we can talk about some of your current research we did speak a little bit about your Alzheimer's work but are there any other works which you do with regards to cannabis which you haven't covered which we can talk about so we look at the moments and it my make it even even more complex but we look at the so on the one side we just look in terms of therapeutic aspects of cannabinoids we look at motor neuron disease so we have Mouse models for motor neuron disease um and at the moment we actually expose them to CBD just purified CBD um and different doses to see if these animals have a get some benefits out of being exposed to that the reason is that some of the pathology and some of the changes in the organism when you're affected by motor neuron disease are not that dissimilar to Alzheimer so you also have for example high levels of oxidative stress in the brain you have high levels of inflammation so it could work there as well so we are testing that out at the moment um but just to make it a little bit more complex I have a post-doc who at the moment or one of her research foci is looking at drug addiction and and I'm not talking about THC I have to be very clear here but CBD has been looked at as a potential treatment against drug addiction so she for example exposes animals to cocaine and sees if if you co- treat them with CBD if the tendency of these animals to develop a dependence to cocaine and they develop that normally very quickly if you can reduce this and early research and there are other research just for example in Australia you look at methamphetamine and they look at the effects of CBD there's some research suggesting that CBD is able to be used at least as a um as an add on treatment for people with drug addiction so at the moment that's another path where we look at and it might be that this is centrally regulated So based on the effects of CBD on the endocannabinoid system because that also might get activated by some of these other drugs but it also looks like that it might have effects on the microbiome so the bacteria in your gut and that's at the moment a a topic which is discussed quite widely in the field of brain disorders because we understand more and more that the gut communicates with the brain and it looks like that CBD impacts on the microbiome so the the condition of the gut and the uh bacteria in the gut and thereby might have a positive effect on the brain which then reduces your tendency to to develop a drug dependence so that's some of the research one of my post is doing at the moment so although cannabis is a drug and although cannabis can induce a dependence in some form certain ingredients of the cannabis plant actually might be able to combat that but again stress here that most of the Cannabis people would use is very low in CBD content so it really depends on what uh cannabis strain you are talking here about and we really look at the purified CBD compound we are not looking at cannabis extracts we take CBD inject it into mice and see how they then respond to in in our example cocaine yeah no I feel I feel I've heard of that though uh of oh yeah of somewhere of uh Cannabis being used as a treatment for addictions before so I'm pretty happy that I it wasn't just like a fever dream and you're someone's actually doing work on it and there is something yes there are people who do it in humans as we speak yeah that's correct but I said it's it's in most cases it would be a CBD compound it wouldn't be cannabis extract

uh Terise do you have any final

questions uh no I'm good that was it's all been really interesting as someone who's not a a um mice person a rat person rat researcher um it's yeah it's all like so interesting um and thank you so much for letting me be able to sit in and um hear about your research yeah thanks for inviting me I I I really enjoyed I said for for some of the basic around um cannabinoid biology you you probably talk better to someone who who is a cannabinoid researcher which I'm not I really I just look at it from this is one of of different forms of medications out there is there evidence or is there any reason that we should look at that and test it in clinical trials that's obviously always the reason why you do mouse research people initially when we started with this research 20 years ago and obviously you need funding for this so we went to funding bodies and tried to convince them to give us money to look at cannaboids to look at their effects on Alzheimer's and we got knocked back for the first five or six years and then when the medicinal cannabis discussion came on in Australia and and and the legislation changed and suddenly that became a yeah that's a logical thing you should test and so we were able to get some funding to test all of these different compounds and doses in our animals but that's really only done to give some evidence to clinicians to be able to then run clinical trials and that's and I just looked this up before our meeting um that is currently happening so in Australia as well as in the US people look at CBD people even look at THC again why would they do this um THC can help with some of the agitation and some of the other symptoms Alzheimer's disease patients show at very late stage Alzheimer's and then so here coming back to your question at that stage if they experience a little bit of a high because of THC is probably not that relevant it is more relevant that the overall life quality at the end of of of unfortunately their disease progression is improved and therefore people are happy to test it out so at the moment there are quite a few clinical trials in the US looking at THC but also CBD in the context of Alzheimer's and how it might help with some of the psychomotor and agitational uh um issues patients experience at late stage Alzheimer so we just try to trigger those developments and you have to test somewhere or you have to start somewhere and that's why we we start with the mice being very well aware that this is obviously a limited model compared to what you then later on would do in

humans uh speaking of uh speaking of treatments there's another treatment which I've heard of which is common um but you didn't really mention it and that was in cancers um it's as far as I've heard isn't well I don't know which strain is considered to be useful in it but cannabis being used in cancer treatment to some extent as well that is true but there again it's really important that you reads the the fine print because a lot of these treatments are more to stimulate appetite in cancer patients when they are going through chemotherapy to help with the pain and the the the feeling sick um so it's not necessarily to treat the cancer it is a lot of times to help the the the overall life quality and the life condition of people who are going undergoing chemotherapy at the time there is some evidence that cannaboids might be able to reduce cancers but a lot of that is in vitro so not even in a mouth model yet so that's in as you know that's in in cell dishes so they have cells which develop cancels and they treat these cells with cannabinoids and the cells then recover better or are able to be protected against a cancer insult that hasn't re really been followed up comprehensively in Mouse models or humans yet so when you when you see that it cannabinoids are used for cancer therapy a lot of times it's actually to help is some of the symptoms based on the chemotherapy it's not necessarily to treat the cancer itself I have to be very clear here because I see all these news flashes as well and then when you actually go into the Publications you can see that it's either in vitro work so in a in a dish or it was really around some of the detrimental um negative effects when you go undergo chemotherapy but it is true it it is used in that we got awesome I think yeah I think we can essentially end there um usually for the last bit we do a few just general quick fire questions but I am not sure how much time you have uh five more minutes if that's okay five more minutes all right uh TR should we ask like three questions each then and can end there sweet awesome so ter you can ask the first one um Sumer or winter summer um movies or TV shows

movies um if you could live anywhere in the world where would where would it be Australia where I live right now oh fair enough uh which super power would you like to have o i discuss this a lot with my with my kids would be flying or because I'm a scuba diver I would be able to breathe underwater if that's a superpower that for me would be a Super Bowl one of the two that's nice probably flying I don't

know um arguably the most important one uh cats or dogs you we have to cats which doesn't mean that I don't like dogs I like dogs a lot but our cats wouldn't go along with dogs so cats awesome um and then the last question which we asked everybody if you had to leave our listeners with the piece of advice uh what would it be Darry can you say that again I didn't hear that if you have your so so if you have to leave us and our listeners with one piece of advice before you leave what would it be pay attention to what cannabis uh you are accessing in case you have a reason to access Cannabis not every cannabis is the same fair enough that's good uh thank you so much J thanks t for joining uh and thanks everyone for listening see you guys thanks for having me much appreciate it I hope you can can make something out of it I know I have a strong German accent so um yeah I'm not offended if you cut it down to three minutes that's totally up to you no it it's it was great I'm sure it'll be absolutely fun right take care guys thank you