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The Use Of Medicinal Cannabis In Oncology with Danielle Brown

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The Use Of Medicinal Cannabis In Oncology with Danielle Brown

What does the evidence say about using medicinal cannabis in people with cancer?

In this episode, naturopath and researcher Danielle Brown discusses her research in using cannabis in oncology, informing us about dosing and which forms of cannabis to administer in which situations. She also discusses the stigma surrounding the medicine, as well as a look into the potential future of medicinal cannabis. 

Covered in this episode

[00:40] Introducing Danielle Brown
[01:37] Anti-cancer actions of cannabis
[03:13] Autophagy vs apoptosis
[05:20] Hesitations for use of medicinal cannabis
[09:00] The difficulties of dosing and prescribing cannabis
[12:18] Intratumoural dosing of THC
[15:39] Dosing strategies
[20:34] Cannabis is not one medicine
[22:17] Physicians and medical cannabis
[25:25] How different preparations produce different actions
[27:45] How evidence can be improved
[34:17] Clinical interactions
[35:55] Administration and absorption of cannabis in oncology
[37:59] Cultural and generational attitudes towards medicinal cannabis
[39:45] Red flags
[41:02] Looking to the future of cannabis
[45:40] Tolerability and dosing
[48:43] Information and further resources


Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining us on the line today is Danielle Brown, who is a naturopath, an early career researcher, completing her honours in 2019, investigating the absorption of medicinal cannabis in patients with glioblastoma multiforme. Her research journey has taken her overseas to present at international conferences, inspiring further study in integrative oncology. Her previous profession as a sustainability practitioner has inspired further research into environmental drivers of health with a focus on the light environment and circadian biology. Danielle's clinical interest is in integrative medicine and, in particular, supporting patient-centred outcomes in cancer management through an informed evidence base. Welcome, warmly, to FX Medicine, Danielle Brown. How are you going?

Danielle: Hi, Andrew. Thank you for that welcome. I'm good, thanks.

Andrew: We're talking about medicinal cannabis. And I saw your poster at the recent NHAA, Naturopaths and Herbalists Association of Australasia, Centenary Conference 2019 and it was on the medicinal actions of cannabis, anti-cancer actions of cannabis. So let's talk about these. What are they? Because we talk about cannabis ameliorating symptoms, but not a direct anticancer action.

Danielle: Yeah. That area is still, you know, very much in its early explorations, I think, in understanding what the mechanisms are. But there's a broad range of mechanisms being identified as such as anti-proliferation properties, your anticancer, apoptosis and autophagy, and then they have all their really fantastic biological pathways they're developing constantly kind of, I guess being elucidated on how it is that it's functioning in the body to get these outcomes. 

But in saying that, this research, I think if there was a paper and right about in the mid-'70s, early '80s, that that was the first time they investigated anticancer actions of medicinal cannabis in a trial, it was. So it's definitely why we say it's not, you know, we're still foundations in trying to understand what these actions are. It's something that has been identified much earlier than today.

Andrew: Yeah. You mentioned autophagy and apoptosis, and they're sort of kind of like along the lines but not quite, can we go into that a little bit and just clear up what exactly are they and how are they different?

Danielle: Yeah, yeah. So in my understanding, apoptosis is when the cell is, you know, triggered as being mutagenic or, you know, not functioning in its correct manner and then the cell will lys and then be collected up and taken away by the immune system and so on. Whereas autophagy more is that element where it can come in and recycle certain parts of the system. I think that's from my understanding, does that sound correct?

Andrew: Well, yeah, to my understanding, which is probably less than yours, but, you know, this is very interesting to me with regards to the stress response, whereas autophagy is initiated to recycle, is it malfunctioning component or is it just extra components? Unnecessary components? I don't know the actual mechanism of autophagy.

Danielle: I think in the beginning, probably figure back when I first came into this subject and did this giant review on looking at medicinal cannabis use in oncology is a broad factor from 1970s on to 2017. We did pull out, working with different people at Endeavour College. We pulled out a few different elements trying to understand what are these pathways, what are the proposed mechanisms and how does autophagy change from apoptosis? Yeah. I can't really talk specifically on that. It gets a little bit out of my realm to be confident in understanding the difference, whether it's, you know, but it is, I think that's the split is apoptosis, you know, we've got to get rid of the cell. Autophagy is that ability... different triggers that then allow that cell to break down in a way that's not as apocalyptic, I guess, as apoptosis.

Andrew: Yeah. You know, we know about medicinal cannabis...I mean, it's so controversial, even though there's a hedge towards the positive, but it's not without issues. Certainly, historically it's been lambasted and treated incorrectly and marketed against. But why is there a hesitation, overall, for its use still in medicine today?

Danielle: Yeah, that's a fantastic question, that one, and one that can definitely be unravelled over and over again. 

Andrew: Yeah.

Danielle: Yeah, I think...you know, from what I've read and my experience reading through the literature, there are times when there is...you do have to take a precautionary approach and know that this medicine isn't for everyone. It's not a panacea. And I think the approach…caution…having hesitation is potentially a good way to go ahead rather than going in full  ball and then getting, you know, adverse events or side effects coming out later on. But, of course, there is that broader context where it has been stigmatised, you know, in the past. And there was actually a really interesting paper that, not a paper, I was listening to a podcast. It was a bit philosophical, but they were talking about sitting in with ambiguity and being okay with sitting in that unknown and uncomfortability of it. 

Andrew: Yeah.

Danielle: And I think it's difficult when you're looking in the medical model to sit with the unknown. So that's why I think the hesitancy is there because we're going, "Oh, what about the evidence base? What does the evidence tell us?" and you know, yet we can look at the evidence and still there's a personal experience of the doctor that's prescribing or he has the intention to prescribe that will take their personal experience into, obviously, you can't get away from your own values, into consideration when looking to treat a patient with medicinal cannabis. So then you've got this double entendre, you're like, "Well, here's the evidence" and like, "Oh, hang on. There's a bit of values that I'm not happy with in using this for this person." So, it kind of...

Andrew: Yeah. It is such an emotionally-charged issue, isn't it?

Danielle: It really is. Yeah, yeah.

Andrew: When we looking though at, you know, maybe a physical hesitancy for its use what about, I mean, let's say tolerability with somebody undergoing cancer therapy who's got raised liver enzymes, for instance, because of the cancer therapy. You know, would that be a reasonable hesitancy for use?

Danielle: I think so, yeah. Absolutely. Absolutely. It's something that has to be considered, I guess. As importantly and in this environment when it is becoming more...people are more aware of it, patients are more aware, practitioners and being able to flag these issues is quite important, you know, such as liver issues and certain enzymes. What's going on there? Is the person, if, you know, in oncology, are they on dexamethasone? Do we have to be a bit more wary and cautious around THC application? There's definitely scopes there, that would hesitate…

Andrew: What's the issue there?

Danielle: I think it's just at a really high dose of THC, you can get some really poor side effects, adverse events. 

Andrew: Yep.

Danielle: But I think that's using THC on its own.

Andrew: As a single entity, yeah.

Danielle: As an isolate as opposed to looking at as a cannabis-based medicine.

Andrew: I was going to ask about that with regards to, I guess you could put this into tolerability or dosing strategies, which I wanted to ask you about next. But when you're looking at a drug, so if you're looking at paracetamol or for our American listeners, acetaminophen, then you've got one molecule repeated again, and again, and again. When you've got cannabis, you've got which cannabis species, which strain, which cultivar? Is it chemically constrained, like you mentioned with regards to high THC or only THC, or very much only THC? Or is it a diverse, more natural product with, you know, lots of terpenes and, you know, what is the ratio of all of these, quote-unquote, “active components?” And I put quote-unquote in there because I think there's so much more than just THC versus CBD.

Danielle: Yeah, certainly. Absolutely.

Andrew: Yeah. But like is that part of the issue with tolerability and, therefore, hesitation of use? Is that the doctors who are prescribing this don't know what to prescribe?

Danielle: Yeah, absolutely. I think so. And, you know, there are a lot of courses out there that practitioners can go along to and get more familiar and understanding of this plant. 

Andrew: Yep.

Danielle: But even then, we're also working with an individual who's going to have different...the endocannabinoid system is going to interact differently. And there's lots of different confounders that perhaps, need to be understood. And so, this idea of, you know, is there a population-based dosing? Like if we go back to Panadol or paracetamol, you know, right? You take two tablets every four to six hours. And when we're looking at medicinal cannabis, it's definitely not taking two drops…

Andrew: Yeah.

Danielle: …three times a day for everyone.

Andrew: But I am very much reminded that professor David Caldecott says, you know, this may seem scary at first, but when you think about how we titrate quite readily, quite freely, quite exceptedly, the use of say, Gabapentin or pregabalin, and we titrate those doses for pain relief…

Danielle: Yes.

Andrew: …then it really becomes, “ah, is that all we do?" 

Danielle: Yes. Yeah.

Andrew: And so, as long as they have an analogy that they're already using, these doctors then seem to become comfortable with, "Okay. So I just need to titrate the dose."

Danielle: Yeah. Yeah. And I think, you know, I'm looking at medicinal cannabis being used in oncology, specifically, we are working with individuals drug doses for the most part…

Andrew: Yeah.

Danielle: …based on body surface area. So it does seem a space where if it's going like medicinal cannabis use is increasing and this area in oncology does provide a platform for it to be comfortable, perhaps, in terms of dosing but you know, then looking at other outcomes such as therapeutic potential and what kind of actions are we driving and whatnot. That's still in development. But I think it's an interesting space to see how it's dosed because potentially, you have the practitioners who are comfortable with that elements of dose titration and going to the individual.

Andrew: Now, you actually covered something very interesting with regards to dosing in your poster that you presented at the NHAA conference, and that was intratumoural dosing.

Danielle: Yeah. So this is a trial done by Guzman and others in 2006, and it was looking at THC being injected intracranially, direct into brain tumours. It's a very fascinating study and of the kind, of course, you know, there's not a lot of human studies on medicinal cannabis. This is probably one of the most recent. So to be able to get in and, you know, directly inject THC into a tumour and look for the responses and then analyse the tumour and different cannabinoid receptors and understand what's happening is very exciting. And it did have, you know, it did have a positive outcome in terms of survival time.

Andrew: Really?

Danielle: You know, it was a very small...you're looking at very small cohort and I think only…

Andrew: Yes, sure. That's a really interesting...it's  really, I mean, controversial, but interesting way of injecting a therapeutic…

Danielle: I know, yeah.

Andrew: …because we know about the issues of therapeutics trying to cross the blood brain barrier. You know, to actually complete that, I mean, that would have been an ethical nightmare.

Danielle: Yeah, I can't imagine. The path that went through that. But yeah, you know, it's pretty exciting though, right? They're injecting it into a tumour, but we are looking at a population that it was a glioblastoma multiforme. So this population, you've kind of, you’ve got to go all out because we've got to survive a time in less than a year and, you know, how are we going to get the best patient-centred outcomes for these people?

Andrew: Exactly. So what were the results? What happened with these patients?

Danielle: Sorry. There was nine in total in part of this trial. And a THC with solution was administered at different times, starting at days three to six after a surgery and it was at a lower 0.3 mils a minute with a syringe pump and it had a subcutaneous reservoir. But ultimately, the data shows that there was an increased survival time. So these patients that received the intratumoural injections of THC. And I think it's important to know that the THC was plant-based as well. Obviously, standardised, but not an isolate THC.

Andrew: So like I'm thinking about the actual preparation of that drug. Like you've got sterilisation issues, I mean, they must've gone all out. This is quite amazing research.

Danielle: It really is. It really is. And I know when I first come across that, I had to double-read it. I was like “intracranial injections? What is happening here?”

Andrew: Which country was that carried out in, by the way?

Danielle: It was in Madrid, Spain.

Andrew: We'll definitely put up the link so that people can read that if it's a full paper. 

Danielle: Yes.

Andrew: Hopefully, it is. Yeah. Real, that's just riveting. But I'm wondering if any subsequent work has been done or are they the only group that's done this work?

Danielle: In terms of intercranial?

Andrew: Mm.

Danielle: Yes. I've not. Definitely not come across any of that. I know there's, you know, there's a handful of trials in motion at the moment, but not using it in this manner.

Andrew: So what else are we talking about with regards to, you know, dosing strategies? What about different types of cancer and looking for different desired effects? Like, you know, traditionally, it's been used as an antiemetic, for instance.

Danielle: Yeah, yeah. So a lot of the data actually will cover looks at antiemesis as an action for medicinal cannabis. And I guess that's interesting, you know, if we go back to the literature review I was part of a couple of years ago, that's yet to be published, but there was a poster and this poster was delivered at the Society of Integrative Oncology, which was really exciting. So we had to get that one-on-one interaction with oncologists who really like they want this information or need this information for patients. But this, again...so if I can introduce that poster a little, it was that literature review. There was a total of 104 papers included in the literature review and 24 of them were human trials and predominantly they were looking at the antiemetic effect of medicinal cannabis and it was across all different kinds of dosings, starting from 1975 through to the late 1990s. And then we have some appetite stimulant actions and looking at the analgesics effect as well. And most of these had really positive outcomes except for the ones that were dosed quite incredibly high and didn't have great patient tolerance. 

Andrew: Aha.

Danielle: So you can kind of understand like, "Okay, that's why you'd get that report that it didn't work as well as it wasn't as effective as hoot because that'll take incredibly high doses."

Andrew: Sorry, can I just clarify that? Incredibly high doses, are we talking about an isolate here? Didn't work? Or are we talking about, you know, overriding some of the pain control systems, say, for instance?

Danielle: So I think for the most part, it was it was looking at THC…

Andrew: Right.

Danielle: …client THC dosing and in capsules. And, you know, going up and above 15 milligrams at one time and in, you know, 4 doses over 4-hour intervals showed it didn't really have the greatest outcomes…

Andrew: Yep.

Danielle: …in terms of patients’ compliance or wants to continue taking it.

Andrew: Yeah. You know, this smacks of what Simon Eckermann and I were talking about his research into...now what was it? And I do have to talk about a product here because that was the focus of the research, but I think it was Epidiolex versus, you know, standard pain therapies for most of this chronic pain that he was talking about? There was a vast discordance, if you like, or a vast variation in costs, which was interesting. But the effect per dose was skewed. It was really quite weird, whereas when you had a much more balanced product, certainly hiring the terpenes and the flavonoids, that it had a much greater effect. Is that what you're coming to the conclusion of?

Danielle: Yeah. The literature is definitely reflecting that, you know, your cannabis space medicines, which are the whole plant extract that has all the elements, you know, you've got your key cannabinoids and then play then flavonoids, as you said, and terpenes. And it's showing that in terms of patient compliance, the cannabis-based medicines from a whole plant are much more tolerated and, therefore, you know, you can argue that if they're more tolerated by the patient and you're using this product in a clinical trial, then perhaps, the efficacy of that would be you get much clearer representation than if we're using an isolate that doesn't have the best tolerability, but however, is termed as medicinal cannabis and then that steals into the knowledge that that's a database and you've got this skewed data where you know, this group A medicinal cannabis and group B had medicinal cannabis, and one was plant-based extract and one was an isolate. And you've got these different tolerability's and outcomes. And I think that's coming back to that first point, why is there hesitation when we've got doctors telling that's not specific and it's, you know, what client have we used? What have we done? What's in it? 

Andrew: Yeah.

Danielle: Then you're going to get confusion around how can we use this medicine when there's no really any congruency?

Andrew: Yeah. I think we need to be mindful that this is, of course, not one medicine but a group of medicines in one plant and we need to be informed about all of these constituents so that we can make an informed treatment decision.

Danielle: Yeah, absolutely. Absolutely. And I think I get a little bit of a bone to pick about when people say medicinal cannabis isn't it a medicine once you standardise it... there's a little bit of like, "Oh, hang on." You know, acknowledging my own bias as a naturopath and we're working with herbal medicine. It's a plant that, you know, it's only through us and as a way to understand what's happening, we standardise and label something…

Andrew: Yeah.

Danielle: … the outcome. But, you know, there's so many other factors as well. You know, we can see from the research from Didi Miery…

Andrew: Yes.

Danielle: … and what he's bringing into the field is outstanding and, you know, moving beyond CBD and THC and the likes of this and to, you know, more minor, what is suggested as minor cannabinoids having quite a huge effect, impact therapeutically.

Andrew: And yet, you know, if you wanted to take that to a medical model analogy, it's not unheard of that doctors will given a certain protocol to use certain drugs in a stepwise fashion… 

Danielle: Yep.

Andrew: …or a prioritised strategy, they will decrease a certain drug if it's not tolerated as well. 

Danielle: Yeah.

Andrew: Cancer is a classic example of that. 

Danielle: Yep.

Andrew: Epilepsy is another one. So it's not outside the realms of learning how to do it…

Danielle: No.

Andrew: …it just requires some dedication to say, "Okay I'm going to really jump in here and learn about this stuff because my patients require it."

Danielle: Yeah. Yeah. And I think like there's actually quite a bit of literature around how physicians feel in using medicinal cannabis and whether they're prepared.

Andrew: Oh, well what was that? What was the result of that one?

Danielle: So actually, for the most part, I think this was a study coming out in the U.S. And they interviewed, I think it was a couple of hundred doctors and it was coming through medical school and they were just saying, "What is your comfortability in...you know, if a patient approached you to use medicinal cannabis, how would you feel?" And for the vast majority, you know, I'm going from memory here, it's about 70% or so of the practitioners were not comfortable…

Andrew: Really?

Danielle: …in prescribing medicinal cannabis. And so that's a huge barrier. That's, you know, this was in 2017, I think that was reported. But even through other, you know, reading different papers through the literature, you can see that medicinal cannabis has been dosed at the wrong time and then, you know, were being reported as being ineffective…

Andrew: Yep.

Danielle: …whether you're using it as a recovery, I think it's recovering medication for antiemesis where it actually needs to be given like prophylactically…

Andrew: Yep.

Danielle: …before treatment. So there's definitely like it even if it is being used in a hospital and it's, you know, you've got people... there's physicians and doctors applying it, the way it's being used is also skewing evidence-base again, potentially because we're getting these poor outcomes, but you look a little bit deeper, you're like, "Oh, you're giving it after the person, you know, if they've had chemotherapy, or nausea, and vomiting, then you're going to give it. It's probably not going to have the best outcomes.

Andrew: So prophylactically is really when it should be started, is that what you're saying?

Danielle: Well, yeah, that's generally like the dosing. That's the dosing guidelines when you're looking at it. 

Andrew: Okay.

Danielle: Yeah. It's going to, if you're looking at for antiemetic.

Andrew: Earlier rather than later.

Danielle: Yeah. No, as a rescue medication. Yeah.

Andrew: Got you. That's really interesting. 

Danielle: Yeah.

Andrew: So this really, like, I was speaking with Lucy Haslam about this of United in Compassion, for those people that don't know the famous Lucy Haslam. And she was saying, "This is probably going to be the biggest ‘I told you so’ a moment, of certainly in Australia." 

Danielle: Yeah.

Andrew: It’s probably, you know, we were thinking about having t-shirts printed. Because patients are desiring it. They want their doctors to know about it. If they don't know about it, a lot of them are gonna use it anyway. 

Danielle: Yeah.

Andrew: So it's in the doctor's best interest to know about it. And there are now courses being run by GPs for GPs to know about what is this drugs and how you can best help your patients by utilising it. 

Now, I was going to ask about preparations, you know, like the old way and, you know, I'll go back into my uni days here, you know, it's smoking anything and then well, it was cookies and, you know, so you've got…both of those involve heating and then there was vaping, which was a very Americanised strategy and one which I only learned about after I finished my nursing training. But now, of course, I've been enlightened by this gorgeous young woman, incredibly strong young woman called Morgan Tyler, who has Crohn's disease using fresh cannabis, so there's no high. Now, this was really interesting to me. So the preparation, what do we need to learn about this plant? And how does that affect the actions? What's the research showing us?

Danielle: Yeah. Well, you know, if we go back to those key cannabinoids, CBD, cannabidiol, and tetrahydrocannabinol, THC, those elements, you know, they require heating of some form of decoupled solution to become active and have, you know, the psychoactivity…

Andrew: Yeah.

Danielle: …that’s aligned with those ones. So, you know, field looking at whole plant and you're not heating it and you're juicing it, is that?

Andrew: Yeah.

Danielle: Yeah. So you've got an acid form of, you know, cannabidiol acid, tetrahydrocannabinol acid. The list goes on and, you know, these have therapeutic outcomes as well. It doesn't require the, you know, depending on... I think that's like, it really speaks to the diversity of the plant, the fact that you can use, depending on what your outcome, what is it that you’re therapeutically looking to achieve? The plants, you can use the plant in the manner to get those outcomes. And, you know, that's more we get to understand it through, you know, in terms of Crohn's disease. It seems like there's proof in the pudding there with this young lady having really wonderful outcomes with it…

Andrew: Oh, absolutely.

Danielle: …and just taking the plant and juicing it and not inducing, you know, the decarboxylated elements which then go on and have certain different effects in our body, in the endocannabinoid system.

Andrew: Yeah. now, you know, we've discussed previously about, you know, a population approach to dosing seems not to be achievable, so how can the evidence surrounding dosing be improved? What needs to happen? Do we need to be, you know, like dead in the area? Has the like what is it, hundreds of different times?

Danielle: A hundred and forty-four, last count.

Andrew: Yeah. How do you match that to a patient? Do you do genotyping? Do you do gene SNP testing in a patient? Is it all to do with liver tolerability? Like what happens? What's your thought?

Danielle: I think there's definitely a lot... There's quite a broad field of variables to consider when using this. And I do... You know, this is where standardisation definitely is really, I think an integral approach when we're looking at medicinal cannabis and knowing exactly what we're working with, specifically when we're looking at in oncology, we want to know exactly what's happening. That argument can go across all medical presentations, of course, but there's a lot of different elements. You know, you can look at the pharmacogenomics around the endocannabinoid system, and then somewhere we're getting into SNPs and, you know, there's the... I think it's called the FAAH enzyme, which, you know, we know with CBD it regulates CBD. So if we have a down, if we introduce CBD into the body, it down-regulates the FAAH enzyme which will increase your endogenous endocannabinoids, which has a certain…

Andrew: Right.

Danielle: …therapeutic outcome that we're perhaps looking at. And then, you know, we can also look at... When we're looking at tumours, there's the cannabinoid receptors on tumours, can they provide any kind of idea around what kind of dose we're doing or, you know, what's the approach? What's the ratio of medicinal cannabis that would have the most therapeutic outcome? But then again, the literature says there's not really any congruence in those numbers to understand, "Oh, okay, this is a, you know, we'll go back to glioblastoma multiforme has these cannabinoid receptors." 

Andrew: Yeah.

Danielle: Then that changes again across all different tumour presentations.

Andrew: Right, okay.

Danielle: So it's not something we can rely upon in terms of trying to be a bit more specific on dosing, but definitely, you know, the endocannabinoids, and the enzymes involved in the endocannabinoid system. So we need to look at liver as another element.

But I think at this point, there's a limit in ability to quantify cannabinoids. So if you're looking at the pathology, you know, in terms of pharmacokinetics, which is really important to be able to advise the safety of new medicines, pharmacokinetic trials and they are lacking in this population…

Andrew: Yeah.

Danielle: … in cancer populations, and around some medicinal cannabis. And, you know, there's a few reasons why that is, but even when we do capture it, it's that ability to measure it. You know, we're kind of limited with that can be… It's a sensitivity presence where it's above 50, I think, it's milligrams or whatever it is carried in the blood of THC and you'll get a positive. But if it's below, then it's negative. That's not really going to give us all the information in terms of what's going on in the body. So the pathology is limiting a bit of that development into this area as well.

Andrew: And is that driven by that, you know, previous stigmatisation of cannabis? Are they always concentrating on THC rather than CBD or the terpenes or, you know, the flavonoids? I mean, I know you've got the terpenes, there's a breadth of them, the flavonoids, there's a breadth of them and then you've got these single CBD and THC, but there are a host of other chemicals involved in cannabis. 

Danielle: Yeah.

Andrew: Now, I know you can sort of think, "Oh, well that makes it impossible," but surely, there's some way to make broad groupings?

Danielle: Yeah, I think those biomarkers aren't well understood. I think it comes back to really not... Broaden out the argument again, I guess, you know, the endocannabinoid system was only really identified 25-plus years ago. 

Andrew: Yeah.

Danielle: And so, our ability to understand and develop biomarkers to understand once that, you know, that medicinal cannabis comes into our body and it's metabolised, where is it going and how do we measure that and how do we quantify it in order to deliver a more proficient dosing strategy or if I had a titrate for this outcome? It's just not there at the moment. And I think it's something that is definitely a gap. When, you know, if we can find those biomarkers and get some good testing around it and develop assays that can make this much critic. 

Andrew: Yeah.

Danielle: So you understand like... Because at the moment, with titration, it goes typically to the individual's subjective use. Like you go into your comfortability. If you're taking drops, cannabis oil drops, then you start low, of course, and slowly build up over a week or two to find your tolerability. And, you know, it might be that you have bizarre dreams and you're like, "Oh, that was probably too much. Just drop it down, 0.2 mils" and then that's where you're comfortable. Or, you know, others.... And then you start looking at individual dosing. Then that person A could go to 1.8 mils, person B taking exactly the same can go to 3 mils a day. And they're both presenting the same, you know, we're ultimately looking at cancer, it’s not one presentation, there's things going on, but they have the same cancer presentation, but look at the different tolerability.

Andrew: Yeah. Well, when you talk about what's needed in the future, I think your career is mapped out. That's for sure. When… 

Danielle: Well, I feel like I need to go study pharmacology. That's all instances. I got this, like my toes dipped into it. I'm like, "Whoa, okay."

Andrew: Yeah. Are there any clinical interactions that we need to be aware of if a patient's using medicinal cannabis as an adjunct therapy? Like, you know, we've got, you know, you mentioned dreams, I think we've spoken about was it nausea or something, we spoke about prior where, you know, you'd just gone way too high?

Danielle: Oh, yeah. If you've taken too much and not titrated the dose…

Andrew: Yeah.

Danielle: …you know, I had that awareness on how they use medicine, then there can be side effects. And then in terms of interactions, you know, not a lot has been shown in that area, we have to be mindful of liver function, kidney function, all the generalities around that. 

Andrew: Yep.

Danielle: But yeah, I guess it's like any other...like it's a complimentary medicine and understanding how these broader constituents that come with complementary, how they interact and what's happening specifically in oncology is going to be continuous, I think. And, you know, there is that lack of pharmacokinetic studies when we're looking into this one, but it doesn't mean into medicinal cannabis, but there are, you know, there's evidence that showed people taking complementary therapy alongside medicinal cannabis alongside your frontline treatments in cancer management. And this is not really, you know, a lot of the time you'd get a positive or an additive effect in terms of increasing chemosensitivity, radiosensitivity, things like that.

Andrew: Right. What else was covered on your poster, Danielle?

Danielle: Well, there's been couple of them now. Ultimately, you know, we were looking at the implications around...we broke it down into administration of medicinal cannabis and oncology and the different forms. So we're looking at predominantly through a capsule. There's spray or a mucosal spray, which is usually generally used for pain management, herbal tea and inhalation and, of course, the intratumoural-administered THC, and what was noted across dosing, all 11 studies supported variable doses. 

Andrew: Right.

Danielle: And all studies did use those titration. It's really encouraging to see, you know, and all around these areas definitely developing.

Andrew: Yeah.

Danielle:  But the big gap was that there was the absorption, you know, there was 17 studies reported in this literature review, which is what the poster was on and only four or, you know, actually, three reported any kind of measures of cannabinoid levels. So you've got 17 potential, you know, they're not all RCTs. They're different elements of the evidence of hierarchy, but there was a potential to measure it and it wasn't measured. And so, the encouraging got me, "Hey, let's look at this stuff." 

Andrew: Yeah.

Danielle: You know, it might not be your classic pharmacokinetic study where you're getting blood every hour or every 15 minutes because of the patient population, it can, you know, the ability to get people to sign up and be part of a pharmacokinetic trial, when they're already under a lot of pressure well, you know, there's a lot of medical intervention happening. You might not get those signups. So it might be just looking at it a different way. And I guess that goes into what my thesis is looking at and getting secondary data off the trial happening run by Dr. Janet Schloss at the moment.

Andrew: Got you. Right. You know what? I wonder if that might be different across cultures as well. Like you've got...what was it? Portugal where they have legalised, I think it was all illicit drugs or something, but then you've got Canada that's legalised cannabis. Various states in America have either legalised or decriminalised it, I may have this wrong. And there's different acceptances in various cultures like normalcy of use, if you like. What surprised me was elderly patients suffering pain seem to be quite open. Now, this isn't cancer, obviously, but the elderly patients in pain seem to be quite open to the use of cannabis.

Danielle: Yeah. That's actually something that's surprised me too, I guess in these last couple of years or so, working in this field, having that privilege to sit with this herb for so long. When I've spoken to, you know, that generation, they're the ones really waving the flag and going, "What is the problem here?”

Andrew: Yeah.

Danielle: “Why is this such a stigma?" Like it completely, it wasn't what I expected. So, similarly, as you felt, I was a bit blown away. I was like, "Well, this is great." You know? I think a lot of the tribe going head-on, you know, looking at policy developments and whatnot. And we need people, we need people power and patients and like that drive is there, it's so loud at the moment. And, you know, I think it is really loud for me because that's what I am doing.

Andrew: Yeah.

Danielle: It's definitely making a buzz in the media and, you know, it's a topical issue and highly exciting study.

Andrew: Oh, it's highly topical, highly exciting, the movements that are being made or hopefully being made in Australia. 

Danielle: Yeah.

Andrew: But what about...well, A, the future, like what do you see the future being, you know, given, let's say the feeling of what's going on in the healthcare system. And can I ask you also about any red flags that we need to be aware of?

Danielle: Yeah. Oh, I'll jump to the red flags. I think it's really important to understand that this medicine, it's not for everybody and you really have to understand certain elements, you know, they are the red flags around mental health presentations, if there’s the history of it…

Andrew: Ah, yes.

Danielle: …is potentially the wrong medicine for that person. And it's, you know, ultimately, if you can be guided by a health practitioner while using this medicine, amazing. That's, you know, that's going to give you some really great outcomes, but, again, you don't have... There a lot of people who that there's that issue of compassionate access and people who have worked with this plant so long they understand how to apply it. But yes, the biggest red flag is under saying mental health issues and the risks involved with that. And not to jump in just because you saw that there was an outcome here over to the left, it doesn't mean it's going to be on your path.

Andrew: Yep.

Danielle: And going to, I guess looking ahead in the future, it'd be wonderful to, you know, I think it comes patient… We need to have access, be made accessible…

Andrew: Yeah.

Danielle: …and not there's...it's such a path  now to try and get access to this. I think recently they showed, you know, the majority of patients getting legal access are getting it for pain management and then, you know, second down the list of the… that was about 2000-plus people getting access legally. And then second on the list was for cancer symptoms at about seven, 800 people. 

Andrew: Wow.

Danielle: So it is happening. I think it's, you know, that's exciting to hear but it's also very minimal and I think, you know, definitely from my experience in, you know, just talking with community and potential patients, people like that, they're not able to access it legally. 

Andrew: Yeah.

Danielle: People are still using it. And that gap, like there has to be a way that if, you know, if they're a place where you can go for information if you are accessing it legally...illegally, sorry. 

Andew: Yep.

Danielle:  Wouldn’t it be great if there was a platform you could come talk to and be like, "Look, I've got this? How can I use this to get therapeutic outcomes and not have that stigma around it?" And it does seem a bit like a pipeline dream, obviously, then the plant would be illegal. It would be difficult to sit down with a health practitioner professional and say, "Hey, just got this off the corner. I'm not sure what's in it. Can you recommend how to dose it?"

Andrew: Yeah. That's right. That's exactly right.

Danielle: A bit tricky, but it would be great if there was... I just…I would love that not to be the instance, you know, "Hey, I've got this plant, I don't know how to use it." And then, you know, we've got these systems there, you know, the MS pathology systems, the MSGS.

Andrew: Mass spec?

Danielle: Yes. Mass spec.

Andrew: And gas chromatography, right?

Danielle: Yeah. To be out, like imagine if you could get something and you're, "Oh, my goodness, I don't know what's in it." And you can take it to a place and they go, "We'll run that for you. And we've got these really quick tests that don't cost a lot" And you're like, "Oh, it's got this, this and this in it and you should dose it this way." Oh my goodness. Amazing.

Andrew: And by the way, it's being sprayed with the, you know, umpteen different pesticides so I wouldn't touch it.

Danielle: Yeah, don't talk about that. That's far too complicated. We're already complicated enough.

Andrew: Well, that's a real issue, isn't it.

Danielle: It really is. It really is, looking at those environmental aspects of the plant. And I think it was mentioned at the United in Compassion conference looking at, you know, ultimately the most cost-effective way to grow medicinal cannabis is outside in the environment with the sun, less use of pesticides as opposed to, you know, putting it in a little warehouse with controlled lighting and, you know, you'd have to then spray it to keep certain bugs out. And I think that was...was that Eric Eckermann?

Andrew: Simon. Simon Eckermann.

Danielle: Simon. I apologise. Yes, Simon. He was mentioning that. And I was just like, "This is fantastic." Like economic.

Andrew: It could be a cash crop which could save Australian farmers.

Danielle: Yeah, the economic model is there. It's just, you know, breaking down these barriers around, you know, policy and different... You can't take the human factor out of it and the values that each person will have. So you were taught political, we're talking about values and policy. We're looking at values. So I don't know, it would be great to have this big flip up the system. 

Andrew: Yeah.

Danielle: Here it is.

Andrew: Wouldn't it be great?

Danielle: I let it rattled all the way back down and, you know, get some symmetry in there.

Andrew: Yeah. Certainly, the practitioners who are willing to prescribe for their patients using the special access scheme, category B, so the SAS cat B, they say now that it's a lot more streamlined than previously, that it's a lot easier to do it, takes only about 15 minutes. This is for our Australian listeners and there, you know, Dr. Teresa Towpik is doing work with the RACGP on training GPs on how to prescribe this drug effectively for patients. And, you know, United in Compassion, obviously, is doing the awesome work in Australia, but there are some other training people around Australia as well. But find out those. 

Just before we get onto further resources, I did just want to ask one point, and it was about tolerability. What about the various products that are on the market today? Like smoking was the traditional way of imbibing this substance and then, of course, you've got baking, and vaping, and we've spoken about fresh juicing, which doesn't give a high. What about these liquids that are on the market? They've been extracted using heat, so they are or can be psychoactive with this THC, but what about tolerability? What about taste, for instance?

Danielle: It's interesting. So I've looked, you know, across different dosaging that's coming from the general market of how you would perhaps take CBD, for instance. And it's quite different to how it's being used in clinical trials. And I wonder like, why is there a gap like that? You know, it's almost four times as much as what you would take in what's being used in a clinical trial. 

Andrew: Right.

Danielle: So that's something that I found really interesting. 

Andrew: Yeah.

Danielle: What is this knowledge gap? Why is this existing? I don't know. But yes, typically, you know, traditionally, it's been inhalation. And, you know, that's going to get the levels in your body within 10 minutes, you elicit an effect. 

Andrew: Yep.

Danielle: However, when we're looking at an oil, it's going to take a couple of hours for you to get that dose in your body, but it will stay a lot longer. So that's why therapeutically or if we're looking, again, coming back to oncology, we want to keep that therapeutic levels at a steady state dose. We want an oil to carry the cannabinoids, and terpenes, and flavonoids as a complete a cannabis-based medicine into the body and elicit that response. 

Andrew: Yep. Right.

Danielle: Whereas using a whole plant is, I think an inhalation absolutely, if we look at pain management, it's going to get quick response.

Andrew: So I'm going to guess then safer pain management, antiemesis, those sort of things that you need and action right now please, that inhaling the product is going to be the best form, but then patients might well have to balance that out with an overnight dosage of a longer-acting product.

Danielle: Yeah. Again, it really comes back to what the presentation is and what the therapeutic outcomes that are wanted are. Certainly, it has been, you look back in the '70s and '80s, the literature into the '90s, it's inhalation. It's being provided cannabis cigarettes and using it in oncology…

Andrew: Yeah.

Danielle: …it’s inhalation and you perhaps won't get that quicker response. So if you're feeling unwell, maybe that's going to work for you. Again, we come back full circle was individual…

Andrew: Yeah.

Danielle: What might not work for you or it might work for them and not the other person. Yeah.

Andrew: We certainly need a lot more information, but where can we get further resources on this, Danielle?

Danielle: Yeah, I think, you know, United in Compassion Australia is a really great resource to jump in and really, you know, get it, get an understanding of what's happening in terms of access in Australia there's certain, you know... I think the first point, of course, would be if you're looking to use this medicine, speak to your GP, and that's probably the best that the first point source, I think, or, you know, your trusted health professional, someone you know who can guide you into the right direction. There's certain cannabis access clinics and what not. So in terms of getting access, that would be the point I look for. But if we're looking into the research and whatnot, just put it in Google. You'll get a ton of papers in medicinal cannabis in oncology. And really, you start your kind of rabbit hole down there. It takes you all kinds of layers, but it's absolutely fascinating.

Andrew: Absolutely. Danielle, thank you so much for taking us through. I mean, it is a rabbit hole, yes, but it's a necessary rabbit hole, which patients are crying out for in need. And they certainly want this and they want their healthcare practitioners, their doctors, their specialists to be empowered, and armed with knowledge rather than a stigma. 

Danielle: Yes.

Andrew: So I really urge our healthcare practitioners, I would say all healthcare practitioners out there not just GPs, but naturopaths, herbalists, everybody really needs to know about this stuff…

Danielle: Absolutely.

Andrew: …if you want to help your patients with these conditions, which cannabis has shown to be of use. But thank you so much for joining us on FX Medicine today.

Danielle: Thank you for the opportunity. It's been a pleasure.

Andrew: This is "FX Medicine". I'm Andrew Whitfield-Cook.


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