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Cannabis Phytomedicine | Part 1: Responsible Clinical Use

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Cannabis Phytomedicine. Part 1 - Responsible Clinical Use

In this podcast Justin Sinclair discusses the therapeutic potential of one of the most important medicinal herbs, Cannabis.

This two-part series takes us through the history and extensive health benefits of medical marijuana as he dispels the many myths surrounding this controversial plant.

Justin's extensive knowledge of phytochemistry and pharmacognosy informs the listener of the wide medical potential Cannabis has for treating many chronic illnesses, offering hope for patients whose current medical therapies have little to offer.

   

Covered in this episode

[00:37] Welcoming Justin Sinclair
[02:15] Introducing the topic: responsible use of cannabinoids
[02:38] The history of cannabis use
[09:54] Is cannabis a gateway drug?
[12:55] Considering cannabis related psychosis 
[15:09] The case for not standardising single actives from cannabis
[17:27] Phytochemistry of the psychoactive components of cannabis
[19:59] Cannabidiol and its actions
[23:23] Dosages and the different methods of consumption
[29:17] Activating cannabinoids by decarboxylation
[32:38] CBD and its anti-seizure effects
[34:29] Decriminalisation of cannabis in some parts of Australia
[38:06] Recreational access vs medical access
[40:30] The issue of substance abuse
[41:32] Discussing the next steps in legislation and Government policy
[47:21] Three caveats about medicinal cannabis that everyone should know
[52:42] Thanking Justin and final remarks


Andrew: This is FX Medicine, and I'm Andrew Whitfield-Cook. Joining me on the line today is Justin Sinclair. Now, Justin's a practising naturopath, author, consultant and lecturer, specialising in herbal medicine and phytochemistry. 

He spent much of his younger years travelling, and learning from different cultures about their ethnopharmacological uses of various plants, which led him to formal study in the complementary medicine field in his 20s. And after completing a Bachelor of Health Science in Naturopathy with the University of New England, and diploma-level studies in Herbal Medicine, Naturopathy and Nutrition with ACNT in 2002, he went on to study the Master of Herbal Medicines with Sydney University's Faculty of Pharmacy, graduating in 2004. 

Key areas of study in this program were analytical phytochemistry, pharmacognosy, toxicology, pharmaceutical technology, and medical botany. He's published on the topics of pain management, herbal drug interactions in peer-reviewed texts, and he's held executive director and examiner positions on the board of directors for the National Herbalists Association of Australia, that's the NHAA. 

Justin has keen research interest in medical cannabis for the last six years, in particular the endocannabinoid system, constituent synergy, ie. the entourage effect, novel drug delivery systems for cannabinoids and terpenes, and the use of medical cannabis for pain, anxiety and immunomodulation. 

And I truly welcome you, Justin, to FX Medicine.

Justin: Oh, thanks so much, Andrew. It's an absolute pleasure.

Andrew: Now, we're going to be talking about a huge topic here, the responsible use of cannabinoids. And I think I'm going to warn our listeners now that we'll probably break this up into at least two podcasts because there's such incredible depth and breadth of information. And I know you're the perfect person to delve into this, so let's get started, huh?

Justin: Sounds great, Andrew.

Andrew: So it's obviously a topic full of contention, legal issues and moral issues. Can you first take our listeners through what exactly are these issues, and why do they make people so heated?

Justin: You know, that's a really interesting question. I think the main reason for contention, in my honest opinion, is pretty simple. I think it kind of boils down largely to ignorance, and a rather large helping of misinformation that exists out there in the public domain. 

It's an incredibly multifaceted, complex topic and when we start to think about this plant, it's incredibly, you know, chemically complex and has so many different pharmacodynamic properties. When we start to look at different literature, the plant itself has anywhere between 400 to 600 different chemical constituents, and only about 60 to 70 of those are belonging to these actual cannabinoid class of medicine. 

So when we start looking at this over time, in all of my years of studying in the field, which is not as extensive as certainly other academics that are out there, it's probably the most chemically sophisticated and broad-ranging therapeutic herb I've ever come across. 

So I mean, if I can just digress for a little minute to answer your question about contention, I think if I can just take a quick stroll through cannabis history, that might actually set the stage a little bit for it.

Andrew: Yes.

Justin: So I mean, if we delve back, cannabis is obviously recognised as one of the oldest domestic plants in the history of mankind. So I think it was academics like Schultz and Molen actually suggesting that it goes back about 10,000 years. So, that's 10 millennia, you know? I mean, that takes us way back to the Neolithic period. 

But that's not provable, and so what we actually have hard data on is, they've found cannabis resin in tombs in central China, buried with shamans, and I think that was radiocarbon dated back to about 2,500 years old. Going further back, we can actually go and see, in areas of Turkistan, I think it was, in China that hemp ropes and fibres have been found about 4,000 BCE. 

So whether or not the psychotropic effect of cannabis was actually going back that far we don't really know for sure. But what we do know in written evidence is that one of the first places we see it was actually in the pharmacopoeia that was produced by Emperor Shennong in the TCM histories. And that was about, going back several thousand years. 

The Assyrians have used it, the Indian Vedas recorded the use of cannabis, I think they talked about it being useful as an appetite stimulant, and also in cases of mania. Now, you can go to India even now, and get cannabis from the licensed bhang dealers, I think it's called over there, so it's like a little drink that they make up. The Greeks used it, Galen wrote about it extensively for its use, I think particularly with the seeds as being intoxicating.

And basically right through our entire medicinal history, all the way up until the European colonies and Americans, right throughout Europe and the American colonies, all throughout, it was listed in the United States Pharmacopoeia. 

And all of this, basically for these 10 millennia, we've been using this plant for all sorts of different actions, whether they're entheogenic, where it's actually been used...I think that is a fairly new term, is entheogenic, which I think literally translates as "generating the divine within." 

So, this is kind of that spiritual and shamanistic application, or whether it's just, the fibre that comes from the stem, the food, and the oil from the sativa seed, and the medicines from the trichomes. I mean, this all has been going on nonstop for 10 millennia, and suddenly in 1937, it stopped. And that's where things start to be, I guess, a little bit contentious, and this is starting to set the scene for this contention.

So you've got 10 millennia of humans using this for the diverse product that it is, and then around about 1937 in the USA, they passed the Marijuana Tax Act. Now, this effectively made cannabis... I don't like the term marijuana, so you know, cannabis is the plant's name. 

But this effectively made it illegal to grow it, sell it, buy it, or distribute it, okay? So the year before, interestingly, I think the large, anti-social propaganda movie "Reefer Madness" actually came out, and that was where it was a pretty large-scale campaign, basically saying how dangerous cannabis was. And I think that did set the scene for negative...you know, well, not negative influence in public, influencing the public view of this plant.

Andrew: Why did that happen, though?

Justin: Well, you know, there is interesting discussions out there about all different types of… you know, some things are a little bit conspiratorial, and others are, whether or not they started to actually understand how excellent this plant was, and there were financial or more pecuniary interests. But I don't know. I simply don't know the actual facts about it. 

But yeah, there's a lot of different ideas about what could have been behind that. But it started in the US, and then it kind of blew up from there. So much so I think it was that then in the '60s there was a law passed, the Single Convention on Narcotic Drugs came into being. 

And that was actually an international treaty, so that inhibits the supply and production of narcotic drugs like opium and things like that, and the World Health Organization put cannabis in there as well. So that placed restrictions on cannabis cultivation, exactly the same as it goes for opium. However, licenses and things like that could still be obtained for medical treatment or scientific research, which at least was a good caveat.

Andrew: Yeah.

Justin: And then we go into the '70s, cannabis has been classified as a Schedule I drug in the United States, and in Australia, of course, we kind of followed suit. And the Schedule for the Uniform Standard of Drugs and Poisons, which it was back then, which is now the SUSMP, actually scheduled cannabis and cannabinoids as both schedule 8 and schedule 9 substances. So these were substances with high risk of addiction or abuse, or substances that were considered criminal or illegal. 

So whilst it's nice to see, just on an aside, that the SUSMP has recently undergone reclassification for certain cannabinoids and moved it from the schedule 8 down to schedule 4, which is prescription only.

I still don't think it's enough, in my opinion. And that's largely just because I'm a firm believer in full plant extracts and full-spectrum extracts, and that whilst some isolated constituents are showing some benefit in some of these studies, I think we're going to get far more benefit from a full-plant extract.

So, that kind of sets the scene for where we are now. So for discussion, your original question, why is it such a contentious issue. And I think one of the first points we need to cover is that there is evidence out there, and a lot of public information suggesting that cannabis is a gateway drug, and I'm sure you've heard of that.

Andrew: Yeah.

Justin: All right. So if we look at this, whether cannabis actually leads to doing harder drugs, you know? So if I smoke cannabis, does that increase my likelihood of doing things like cocaine, heroin, methamphetamine? 

Now, there is some evidence in the literature to suggest that, yes, that could be the case, okay? But as most of us know, at least in the field of science, correlation does not imply causation.

Andrew: No, that's right. Yeah.

Justin: So, we need to start...yeah, we need to start to consider other things. There is a growing body of research actually showing that poverty and poor socioeconomic status is a much stronger predictor for progressing into hard drugs, so that leads to the...

Andrew: Oh, really?

Justin: Oh, yeah. No kidding, you know? Like, why can't they actually separate these variables out I'm not entirely sure. Then there's the other aspects, simply association with people that use hard drugs increases risk factor for you using it, that's regardless or not of whether you've smoked cannabis before. 

And then I think a much more important impact, or discussion actually, is mental illness. So if you've got pre-existing depression, anxiety, bipolar disorder, any social personality, schizophrenia, these do predispose some people to use harder drugs.

Andrew: Yeah. They also predispose patients to chronic smoking.

Justin: Yeah, and that's dependence. And that's another very important point for contention, which I'll certainly discuss. That's an absolutely key one. 

And then I guess, lastly, on that final concept of cannabis being a gateway drug is, well, we have to consider research which has suggested that criminalisation and prohibition actually are real gateways to harder drugs too. Because if you're not making it available for the public, then they'll just go underground and find other things.

Andrew: Black market, yeah. Yeah.

Justin: So I mean, if we start to think about this, I can actually give you some examples, with recent legislation changes in the United States, particularly where they've actually legalised… So we're not talking about decriminalisation, they've actually legalised cannabis, such as in Colorado. They’ve actually found that crime has not increased at all in these areas, and it's actually gone down. 

Interestingly also, is that opiate overdose deaths have gone down as well. Now, I heard a disturbing figure from a doctor just last week, that there are 46 deaths per day in the United States attributed to oxycodone abuse.

Andrew: Yeah.

Justin: So if we just kind of ruminate on that figure for a minute, that's a very important point. So this, we can talk a little bit later if we have time for decriminalisation and legalisation, but I think these kind of statistics and discussions need to be considered whether or not cannabis is a gateway drug at all. So obviously, more research needs to be done. 

Then we get to another contentious issue, which brings us up to psychosis, okay? So, this is something that needs to be considered, cannabis-induced psychosis, but we need to kind of think about this rationally, and not turn the baby out with the bathwater. 

We need to consider things like individual neuroplasticity, individual genes, polymorphism, are there any pre-existing mental health problems, and also the phytochemical concentration of the different constituents within the specific strains of cannabis they're using.

Andrew: Yeah.

Justin: So I mean, just for example, the tetrahydrocannabinol, which is the main psychoactive component of Delta-9, is in THC. That's what that is in dominant strains now, in such as one particular strain called White Widow. So through selective breeding programs are far stronger than the cannabis of the 1960s. So you know…

Andrew: Oh, really? Even stronger than the hippie generation?

Justin: Oh, hugely.

Andrew: Oh, right.

Justin: So if we start to look at that, with these high THC varieties like White Widow, some are reaching into the realm of actually about 20% THC. When back in the 1960s it was literally around 3% to 5%. 

So, these high THC strains do have the ability to cause dysphoria and potential psychotic episodes. But if it was actually paired… and by this, by pairing I mean selectively bred in. So instead of just being pure THC, if we could also put smaller amounts of CBD in a cannabidiol, then what we'd actually find is that that can cannabidiol with that will antagonise the dysphoria, and this has actually been shown in certain studies. 

So the CBD itself, other constituents within the plant will actually reduce the potential for psychosis. So this kind of… when we start looking at single active substances like Marinol, the Marinol capsules which have been quite popular in certain studies, like… I think they also call it Dronabinol, and this is basically just a synthetically produced Delta-9-tetrahydrocannabinol. They're not patient favourites. Patients don't quite like them because the therapeutic action, it just comes from one single cannabinoid, and they actually start to get a lot of adverse effects. 

So I think as soon as we start isolating, we lose therapeutic potentials…

Andrew: Well, how often have we heard that?

Justin: Yeah, exactly. And this is exactly why we need to get the legislation and regulation for these medicinal cannabis products right. I don't think we need to just be focusing on single actives, we need to understand that the herbal synergy, or what they call the entourage effect…

Herbalists and naturopaths know the concept of herbal synergy well. One plus one doesn't equal two, it actually equals three, or sometimes four. So, certain combinations of these constituents are going to augment and strengthen each other's effect. And when you're talking about, you know...or even antidote each other, like I've just mentioned with CBD and THC. 

So, the term that they like to use in the medical cannabis community now for this type of synergy is known as the entourage effect. So it's not just one constituent, it's an entourage of them that actually exhibits this. And this basically supports, at least in my mind, whole plant, or what we call full-spectrum extracts when it comes to...

Andrew: Absolutely.

Justin: You know, we can still allow some standardisation of major cannabinoids like THC and CBD, just like we do in liquid extracts in herbal medicine. We just don't isolate them. And we can...you know, otherwise we miss out on all sorts of other important constituents, like terpenes, and things like that.

Andrew: Well, I think the issue, one of the issues there is that once we isolate an active, we're talking about a drug.

Justin: Exactly. And that's exactly what things like Marinol, Sativex, Petadolex and things like that are. And that does not mean that they don't have benefits, because they certainly do, but I just, I really think it's important that we explore full plant extracts more. 

Andrew: Yes.

Justin: Because just in my clinical experience... And by clinical experience, let me just explain that, I have seen and worked with patients over in the United States about this, where it is obviously not criminal, like it is over here. 

So it's not something I've taken part here in Australia, but I have spent time with cannabis physicians, dispensaries, and large amounts of patients over in the United States, that have used various types of cannabis. So, that's just that experience coming through there. 

So yeah, it’s... I just would love to see the government actually explore that, and not just explore single actives. So, we've covered...

Andrew: Hmm. Can...

Justin: Sorry. Sorry, Andrew.

Andrew: Sorry, can I just go back to a comment that you made right at the beginning when you were talking about the historical use, and the Assyrians used the oil, they… sorry, they took it orally? 

So would you therefore be looking at the use of CBD, or cannabidiol? And the reason I say that is, because is it true that to be psychoactive, Delta-9-tetrahydrocannabinol, Delta-9-THC, doesn't that have to be heated to become psychoactive? Is that right?

Justin: Yeah, look, that's a really good question. And this is all...I guess if we have time to touch on the phytochemistry in a huge amount of detail. But yeah, the concept of heat and drying…
So this is why if you go kind of tiptoeing through the tulips of a cannabis plantation and pull off some nice big, fat inflorescence and eat it, it's not going to cause any psychotropic effect. 

And that's largely because the cannabinoids exist in what's called an acidic state. So if we look at THC, for example, this is your THCA, so tetrahydrocannabinolic acid is what it actually exists in the plant until you dry it, and then eat it, okay?

Andrew: Right.

Justin: So what that means is that the tetrahydrocannabinolic acid has got a carboxyl group, a COOH group attached to it. And basically as you dry it, that starts to weaken the connection, and then as soon as you start to heat it… 

And you know, various heats, I think there are some that are talking about kind of the 120 degrees Celsius for 40 minutes, or 150 degrees for about 25 to 30 minutes, and that will actually snap that carboxyl group off. And now you've got the activated Delta-9-tetrahydrocannabinol, which can bind to the CB1 receptor, and now causes psychoactivity.

Andrew: Right.

Justin: So whether or not they knew about that back in the day, we're unsure. However, they have found samples of hash. And hash is just the pure resin where the CBD, or you know, CBD and all of the cannabinoids reside. So I would actually venture and say that they did know about the psychoactivity, and they knew about it very well.

Andrew: And indeed the activity of CBD, the cannabidiol in the oil, is that right?

Justin: Yeah, well, that CBD is really only something that we haven't known about until fairly recently. I mean, we're only talking 50 years, actually even less. So whether the ancients actually knew about the actual isolated constituents, well, that's a different matter. But I certainly think they used the full spectrum of the plant for different things, and CBD would have been a component of that.

Andrew: So, let's...because we're there, let's briefly delve into cannabidiol and its actions, because as you mentioned earlier, it tends to antagonise the psychoactive effects of THC. Is that right?

Justin: Yeah, well, that's one of the things that's said. So, CBD has what they call these antipsychotic effects, because it can counteract the potential psychotomimetic effects of THC in certain individuals. 

But CBD is just, by itself cannabidiol, it's really interesting. I mean, there's a lot of excitement about CBD in the industry and profession at the moment, because it does have all sorts of different actions. I mean, analgesia is just one, antidepressant action has actually been shown in early rodent models. It's an antiemetic, it's an incredibly good anti-inflammatory. 

And the thing that most of us probably know about it is it's anticonvulsant or anti-seizure effects. So they've actually isolated CBD...and this is what I think Epidiolex is, and they've actually used it as an orphan drug over in the United States for Dravet syndrome. And Dravet syndrome, as you know, is a kind of really, really nasty form of epilepsy to a degree, and they've been getting excellent results with it. 

It's also got some antioxidant, very powerful antioxidant effects, and used for the treatment of addiction. Interesting studies coming out about CBD now are also showing benefits for schizophrenia, which is kind of interesting. More research needs to be done, but, you know, about 100 milligrams of CBD is being used for that.

Andrew: Wow.

Justin: And it's also got some antifungal and antibacterial action. So, it's a hugely...I mean, just this one constituent has all of those potential actions. And so when you start to consider that in the full spectrum of the active constituent profile of the plant, that is one of over 400 different constituents. 

So now you're starting to grasp why I just get all hot and bothered over this plant, because it is literally packed full of so much therapeutic potential, it's just not funny.

Andrew: Absolutely. So you know, reductionist though it is, because we're only talking about two, if… what's one of the main issues or possible causes of lack of effect in some early studies using cannabis, was because they possibly could have had too high THC and too low CBD.

Justin: Yes, it's certainly possible. And this is where, again, we're really only starting to scratch our understanding of the relationship, and even more importantly, the interrelationship of all of these constituents, and how they work together. 

So where we're starting to see a problem almost is that by isolating, which is the scientific reduction of standard, by isolating and then studying everything that we can about it, we're just looking at the tree, and we're getting the forest. And so I think this is why I'm trying to encourage as many of those in the scientific community that I can to use the full plant spectrums. Because just what I see with patients is that that's what they go back for every time. They actually try the Marinol, or they try different single actives, and they just get too many adverse effects, and they always get back to full plant extract, and I think that's where the future is.

Andrew: But normal imbibing of this herb has been smoking. That's been the traditional thing, and it's been seen as being bad for the lungs. So, can you talk to us briefly about the different dosage forms, apart from simple smoking? How do people use this, and for what varying effects?

Justin: Yeah, no, look, that's a really interesting question. So I mean, if we look at things like oral use. So I mean, oral use is probably the one that a lot of people use over in the States. And so we're not talking smoking, we're talking about two different methods of ingestion. 

So typically, we're looking at mucosal absorption. So this can be sublingual under the tongue, because remember that many of these cannabinoids are highly lipophilic, so they absorb very, very effectively across bilayers and cell membranes. 

So we've got the mucosal effect, which is going to have an increased kind of absorption. Whereas if you ingested it as a food or edible, as they call it, like a medicinal edible, then that obviously has to go through hepatic hydroxylation. And in some instances, that hepatic cycling or biotransformation can actually make it stronger, but it takes longer to kick in because it's actually got to go through that process. 

So, this is where we start looking at people that ingest it, and then they don't feel anything happening so they ingest more, and they actually have a really bad time of it because they've now overdosed...you know, they've had too much, and they're having a bad time. So, this is where dosage is pretty darn important.

And then we start to look at inhalation, so this is where you've got smoking versus vaping. And so smoking, obviously, is one way that’s been used since time immemorial. There is combustible substance, of course in there, which is not seen as overly good for people that are needing this on a regular daily basis. 

So they've developed vaping, which is basically just exposing the plant material to very, very high temperatures, but not actually causing combustion. And what's really interesting about that is that depending on the actual active constituents that you're after, you can set the temperature, in some instances on some of the more sophisticated vaping devices, to actually just extract those things. 

Andrew: Wow.

Justin: So if it's the terpenes you're after or certain cannabinoids, and you can set temperatures just for that, so you're not getting any of the negative side effects associated with smoking. And then you've got…

Andrew: Sorry. Sorry, Justin, so you set it to stun. So… sorry.

Justin: Yeah, kind of. That's pretty much it, set phasers to stun. And then you've got suppositories. Now, obviously here, there can be fairly good absorption of cannabinoids through the rectal plexus. 

However, the problem is, well, not many people probably want to consider doing that. But for some people it actually works very well, particularly those that are maybe paralysed and things like that, or have problems with digestion or absorption, because they might be on feeding tubes, or something like that.

Andrew: What about a localised effect, say for lower back pain, or say, you know, colon cancer, you know?

Justin: Excellent question. And that's where, you know whether or not it's actually going to be absorbed through the rectum or whether you try and push it in a little bit deeper, it could have very, very good benefits to things like the inflammatory bowel diseases, so things like Crohn's and ulcerative colitis, and...

Andrew: Wow.

Justin: ...maybe even diverticulitis, because it does exert a very strong anti-inflammatory effect.

Andrew: Yeah.

Justin: And then from there, from rectal absorption we go to topical. And topical obviously makes sense because as I've shared, the cannabinoids are highly lipophilic. However, what we don't know a lot about at this time is bioavailability. So a lot more research needs to go in there. But this could be potentially really useful, you know. 

I mean, maybe when someone's having, say an epileptic fit, you can't put something in their mouth. You can't get them to smoke something, you can't get anything in quickly to them. So maybe this could be something that could be used down the track as another novel drug delivery area to actually get into the blood quickly for those that are actually seizing. I mean, there's all sorts of opportunities there.

Andrew: You're bringing back to me memories of when I used to nurse, and we used to have this, the nitroglycerin ointment or cream. And it was measured in centimetres. So you wouldn't give a milligram dosage, you'd give a dose of two and a half centimetres to somebody, and you'd squeeze it out like a toothpaste on this ruler, on a pad, and then just put it on their skin. It was really funny.

Justin: Well, I think that's actually a sign of where we're going to be heading to when it comes to cannabis. And the reason that is, is because you need to individually titrate the dose for the patient, and this is where it's going to cause a lot of… not problems, but a kind of bigger educational learning curve for doctors, if doctors are indeed going to be the ones that are going to be prescribing this in Australia. 

We don't know what's going to happen yet when it comes to legislation or moving forward, but we need to understand that cannabis, with that individual titration, with all sorts of different individual polymorphisms and receptor expression and all that kind of stuff, it's not a one size fits all.

Andrew: No.

Justin: So, we're really going to need to look at individual dosage titration for patients, and that's where it is in America at the moment, they start low work up until they've got coverage, and they titrate it just for that patient. So, but we've got lots to go.

Andrew: But you know, they're even looking at this for drugs like tamoxifen, you know? Looking at different SNPs and cytochrome detoxification enzymes, so that they can see who will tamoxifen work for, and who won't it work for.

Justin: Yeah.

Andrew: So yeah, I think that's just where personalised medicine is going to head. That's just...yeah.

Justin: It has to be. It's got to be patient-centred.

Andrew: Yeah, that's not necessarily restricted to the endocannabinoid system.

Justin: No, not at all. Not at all.

Andrew: But what about decarboxylation used with cannabis? Tell me about this. This is something I'm not familiar with at all.

Justin: So yeah, well, this is kind of an emerging field at the moment where, you know, what we talked about, heating the cannabis decarboxylates it, and that activates a lot of the cannabinoids. So it takes CBDA to CBD, it takes THCA to THC. So, it's an activation of many things. 

But there are some camps in the field of cannabis medicine that basically suggest that raw cannabis actually does the trick too, so you're not actually needing to decarboxylate at all. So in this way, they're just looking at juicing leaves, for example. So anywhere between maybe 20 to 30 leaves a day they put it through, like, a wheatgrass juicer, which actually exerts very, very little heat, because remember that heat is part of the process that can convert these cannabinoid acids into their active forms, and then they're actually just drinking the juice every day. 

And there are...look, there's anecdotal evidence, there's not a large degree of scientific evidence out there at the moment, but certainly clinical anecdotal evidence that people with things like fibromyalgia have been getting benefit from this just from the THCA. So, THCA and some of these acids forms do exert different pharmacological activity. 

And so you've got these kind of two camps that are sitting there going, “Raw is best," and then the other is going to say, “No, you've got to decarb it to get the action.” And I think, if they actually take the time to stand back and look at things in totality, what they'll find is that both have a place. It's not that one is right or one is wrong, it's what is right or what is wrong for that individual patient. And this, again, just goes to show the complexity of the chemistry of the plant, and its huge scope for therapeutic potential.

Andrew: Yeah.

Justin: But not everything necessarily needs to be decarbed or smoked or vaped or anything like that, it can actually still have application, and far less psychoactive component because, of course, remember that THC is the main psychoactive. 

So when people sit there and say, “Oh, my God.” I daresay that's another contentious issue by itself, you know? Cannabis, everyone's going to be walking around stoned. Well, no. 

Delta-9-tetrahydrocannabinol is a psychotropic, but CBD isn't. CBC and all these other types of cannabinoids actually exert no psychotropic effect whatsoever. So what we actually find is that some patients are using CBD-specific strains, non-psychotropic action during the day, and they can still work and hold down jobs and all this kind of stuff. And then they get home, and they're having trouble sleeping, or they're having pain and things like that when they go to sleep, and they're using the THC-specific stuff for that. 

So this is... and apart from that, I mean, we could even go down the road of talking about cannabis actually exhibiting a biphasic response anyway. So you can smoke cannabis, you could ingest it, and you can get initially this kind of stimulatory euphoric type of action, and then it can actually take you down into a more sedating or hypnotic action. And this is all dependent on the strain. 

So when we start to look at the different species and stuff like that, if we have time to discuss that, we can certainly flesh that out more. But that's the level of specificity that we actually have to give the patients, when it comes to this broad spectrum of phytochemical activity.

Andrew: Yeah. What about patients who use CBD alone?

Justin: Just CBD, yeah.

Andrew: Yeah, so what sort of things do you use it for, and what can patients expect in the way of results?

Justin: Oh, look, I think when it comes to the CBD, most of it, most of the evidence that exists at the moment is for seizures and seizure disorders. So this is where we're starting to see a lot of people talking about various types of CBD-rich oil extracts that they're giving to their children, particularly children with things like intractable epilepsy. 

And you know, people are sitting there saying, “Oh, my God, that's so awful that parents are experimenting on their children.” I need to be really clear about what intractable epilepsy means. Intractable epilepsy means that no pharmacological drug in the modern orthodox medical armamentarium works, you know? 

So these patients are trying all of the different drugs, it's not working. So what do they have to lose, really? And we're talking about seeing patients that are having 30 to 40, sometimes up into the hundreds of focal seizures a day are going down to having maybe three or four in a couple of weeks. So this is really where CBD is shining at the moment, in this kind of anti-convulsive, anti-seizure are.

Andrew: Yeah.

Justin: It also, though, as I said, it does have these benefits with anti-inflammatory effects. So a lot of people are, again, taking this kind of during the day for things like maybe rheumatoid arthritis, and multiple sclerosis, or things like that. 

It also has really, really strong neuronal antioxidant effect, and this is something that needs to be looked at a little bit more. But unfortunately, most of the focus for CBD at the moment is kind of wrapped up in seizure medications, or different types of forms for seizures, because it does work quite dramatically.

Andrew: Yeah. You mentioned before about the decriminalisation...or forgive me, the legalisation leading to less crime in certain states. What though, what effect would there be, or fallout would there be, about over usage, you know? Let’s say overzealous usage, and so people being stoned all day, that sort of thing. And loss of productivity, and that sort of thing?

Justin: This is kind of, I guess, a larger social issue, and not one specifically just tied to medical cannabis, of course. So I've been to quite a few medicinal cannabis events over the years, both here and overseas, and one of the things that's kind of interesting about that discussion about decriminalisation is that it, of course, attracts many of those who wish to just see cannabis decriminalised, or even made legal, for recreational use. 

Andrew: Yes.

Justin: And so this is kind of, again, a bit of a contentious issue, where some people say, “Oh look, you know, I'm all for people that maybe needed for medicine, but I don't want people to be able to have access to it," and they are particularly maybe those people that are a little bit more conservative. But already in Australia it's been decriminalised in two state and territories. So we've got...I think, I believe it's in the ACT you can get...

Andrew: ACT and South Australia, yeah.

Justin: Yeah, you can get caught with two non-hydroponically grown cannabis plants. So they've got to be outdoor-grown, or up to but not exceeding I think it is 25 grams of cannabis. So this is just under an ounce, so that's a fair amount of cannabis. And all you have to pay is a fine of $100 within 60 days. 

So you know, it has been decriminalised, but the drug is still considered illegal due to federal laws, but no criminal charges are laid at that point. Hence the term decriminalised. So, why don't we see then huge amounts of people moving to Canberra, I hear you ask, that are needing medicinal treatment?

Andrew: I could answer that, I live there.

Justin: There you go.

Andrew: No, I'm kidding.

Justin: But, you know... I lived in Canberra for a lot of period of time when I was younger. It's a great city. And you know, it's great to see that they have these kind of open-minded laws when it comes to decriminalisation. 

But why aren't we seeing huge amounts of families moving down there? And the simple fact is, is that the amounts that they're actually allowing... You know, when I was talking about to you about, maybe a family is using fresh leaves and they're juicing, you need about 20 to 30 plants to be able to harvest those leaves daily to actually be sustainable. 

And depending on the...you know, you don't know what strains you're getting, and the quality control. You are allowing them to go down there and do this, but they don't actually know what medicinal strains they've got, because I'm sure that the local dealer that they're getting it from may or may not be aware of that. So, this is where this starts up a whole other area of quality control and quality assurance when it comes to good, reproducible results of medicinal cannabis. 

But yeah, you said South Australia as well, they were the first ones, I think. They decriminalised cannabis back in 1987, and they were the first state that did it. And I think they've got a little bit wider scope of allowance. So I think you can have up to 100 grams of dried cannabis, which is a substantial amount of medicinal cannabis there. And I think, yeah, if you get caught with that, it's a similar, type of fine, it's about $50 to $150.

Andrew: And they're actually quite a conservative state. Generally.

Justin: Yeah, which is interesting. And you compare that to New South Wales and Queensland where it's still highly illegal, and you can do jail time.

Andrew: Yeah.

Justin: So I think the concept of decriminalisation does work, as evidenced by particularly, certainly international countries doing so. But I think the discussion is easily hijacked by those wanting recreational access over those that actually require medical access. 

And you know, this kind of discussion that I'm more passionate about in the first instance, is getting the people, the patients that need medical access, medical access now. And whether or not decriminalisation opens up recreational use, that's another matter. My main concern is just for patient care, and so I'm much more concerned about medical access. 

But it's certainly a bone of contention for many in the public. So as I said, particularly those that are kind of more conservative, they think it will increase people being able to smoke recreationally when they might actually not be opposed to the idea of people using it for medicine. 

So regardless of that, I am of the opinion that out of all of the drugs ravaging society at the moment, cannabis is probably the least of our worries. I mean, let's be honest, compare it to things like ice, meth, heroin...

Andrew: Ice is just horrible.

Justin: Or even some of the legal drugs like tobacco and alcohol. I mean, when was the last time you heard of a cannabis smoker lighting up and going on a rampage?

Andrew: Yeah.

Justin: You know? But I think the only thing that's in danger in most cannabis smoker's household is the bloody fridge or the pantry getting decimated when they get the munchies. I mean, when I...

Andrew: I remember an old joke about...what is it? Random drug tests, and they'd bring out a tray full of Snickers bars and paddle pops, and anybody who ate the lot, they were charged.

Justin: You know, I love it. It's just one of those things that kind of cracks me up, you know? Because I mean, look, when I was younger, I may or may not have experimented with cannabis, and unlike Bill Clinton, I certainly inhaled. 

And I can assure you that violence, anger, mayhem and all those types of things were pretty much the furthest from my mind. I was too busy exploring the inside of my navel for two to three hours, or sitting on the hood of my car, looking at the Milky Way. I mean, Ozzy Osborne, perhaps not the best example of responsible drug use I can think of, or even clean living, for that matter.

Andrew: No, that's right.

Justin: But anyway, he once said in a Black Sabbath song called Sweet Leaf that cannabis introduced him to his mind. And I think for many it does. But that being said, of course, it's not without risk.

Andrew: Yeah. Well, the big question there is just like alcohol, the reason of… or the issue of abuse is why?

Justin: Yeah, exactly. And I mean, if we're going to start throwing statistics around, we can start looking at the legal drugs, and just how damaging they actually are. I mean, when we start to consider in 1998 I think it was, over 19,000, Australians actually died of tobacco-related illness. I think that's, you know, kind of obscene. 

I think we're talking about 7,500 people in 2012 dying of diabetes-related diseases. And these are things that are highly dependent. We do get dependent on them. And so, sugar, tobacco, alcohol, whilst they're legal, we're probably actually seeing far more damage through the Australian population, when it comes to morbidity and mortality, from those legal drugs than we would ever see from cannabis.

Andrew: Hmm. But what about caveats? What can you tell us about the caveats of use? And I should point out here that medicinal cannabis use is actually being looked at seriously by the government now. And...

Justin: Yeah, and it's fantastic. I'm so happy to see that.

Andrew: And it is fantastic. I think there was talk once again to grow it in Norfolk Island, so that would be dependent on if it passes through Parliament. But you know, it could actually offer some economic incentives for a population as well.

Justin: Oh, look, I think that's a huge thing. I mean, what's going to happen with medical cannabis I think is a really interesting question. So...particularly regarding government. So if you will pardon the pun, the political propaganda machine really, at the moment, is going to pot over this issue. I mean, so far, all I've seen up until recently is politicians jumping on the medicinal cannabis bandwagon saying lots about assisting patient suffering, but unfortunately, there's not a lot of doing. 

But there was commitment, of course, by various states, which I'm sure you're aware, to consider conducting clinical trials. And now, I think this was a great step forward, but again, in my honest opinion, not spending tax dollars wisely. And still not addressing access of the medicine to the patient. So I actually feel that this money would be far better spent, and this is something I've been arguing with different academics on the topic, in actually forming a committee or a working group of professionals within the medical cannabis community and field from around the world, in countries where it already exists in some working form. 

So I mean, everyone from growers to legislators, lawmakers, judges, cannabis physicians, botanists, taxonomists, herbalists, pharmacologists, pharmacists, the whole lot. Put them in a room, get them to discuss what has worked, what hasn't, what are the obstacles, and what are the solutions? And they can then provide a report to government that can then act on their experience. I mean, we don't need to reinvent the wheel here as it's actually been done successfully elsewhere, but we can certainly perfect it, you know?

And so the other thing that such a group could actually work on, which absolutely baffles me, is how about we sit down and do a literature review? I mean, a full literature review. This would take a hugely long time for cannabis because it's got over 15,000 papers attributed to it in PubMed alone, based over a huge spectrum of different disciplines. 

Andrew: Wow.

Justin: But it does allow us to identify what we need for further researching, and what we don't. I mean, this could actually highlight what conditions could benefit from cannabis immediately, and thus start the process for getting patients access to that drug now. 

So it's great that these states are wanting to move forward with the trial for epilepsy, for example, but there are three studies that have already been done on it. And so whilst a positive result would benefit thousands of Australians with seizure disorders, what about those that have got multiple sclerosis, or rheumatoid arthritis, or suffering from brain cancer, or neuropathic pain, or side effects of chemotherapy? I mean, they're still important, and that trial doesn't include them, you know? 

So I think we need to do a complete literature review as a matter of urgency, because not only could it actually save millions of taxpayer dollars, but more importantly, we can identify very quickly what evidence currently exists for various conditions, and thus bypass the need for further testing.

I also question whether those trials that are actually looking at being done are actually on active cannabinoids, single actives or full spectrums, but I guess that's another matter. But then we jumped forward now to recent news, to that amazing United in Compassion symposium, the inaugural medical cannabis symposium that was organised by that amazing Australian, Lucy Haslam. She's a fantastic advocate for the sufferings of all sorts of different diseases around Australia. 

And I went to that symposium, I had a chance to talk to senator Di Natale of the Greens in person at dinner. And he was talking about putting together this draft proposal which involves creating a new national regulator that works independently, that would oversee everything from the manufacturing, distribution and growth of medicinal cannabis, keeping everything in a nice, neat little department. 

Andrew: Yes.

Justin: And of course, what we see this week is the Liberal government wanting to put their own stamp on this process. They’ve got different ideas. And that's where Sussan Ley, I think she's the health minister, talked about finalising drafting limits for the Narcotic Drugs Act of 1967, which again talks about allowing the growth of cannabis for medicinal and scientific purposes. Which again, is still fantastic because we can look at quality control, we can, you know...

Andrew: Yes. That's right.

Justin: We can then not only start an industry that could be worth hundreds of millions of dollars to Australia. Remember the opium poppies down in Tasmania, for example, that's a fantastic initiative. But it starts growing and delivery, the sustainable, high-quality supply. 

But again, what does it not talk about? And that is patient access to the drug. So this needs to be the critical point of discussion, I think at the moment, for politicians and policymakers right now, is how is that actually going to work? 

Are they going to use medical cards for cannabis, which is utilised in places like California? Who will dispense them? What conditions are going to be covered and included? Should all medical practitioners be allowed to dispense cannabis cards, or only those that have completed a course on the endocannabinoid system, and what strains or dosage forms are good for said condition? I mean, it opens up a wide range of questions that need answering.

Andrew: Wow. Oh, absolutely.

Justin: And quite frankly, I think we need some type of international working group that could advise the Australian Government on policies with this. Because quite frankly, there are very few medicos in Australia that have any experience, practical experience using this plan at all, and that's the facts.

Andrew: So just wrapping up, can you give...there's obviously going to be caveats with use here. And as you mentioned before, there are going to be those people that want to use it for recreational use, and they're going to abuse it, and they're going to run into issues because they've got issues. What sort of caveats... So, sorry, so I'll say to our listeners right now, this is not something that we're recommending for recreational use, this is a medicinal use.

Justin: Of course.

Andrew: But what sort of caveats can you give our listeners if they were using medicinal cannabis, or indeed one of the extracts, like particularly CBD?

Justin: It's an excellent question, Andrew, and finishing up, it's a pretty important one. So the first thing that I need to make absolutely clear is that cannabis is not for everyone, nor is it the panacea that many think it is, okay? 

So I was speaking in a radio interview with a really well-renowned cannabis physician, Dr Jeffrey Hergenrather over in the United States, and he's a cannabis physician practicing over in California, and he's also the president of the Society of Cannabis Clinicians. This guy has got extensive experience in the field of this. And he was quite clear in our discussion, expressing that cannabis as a medicine or even as a recreational substance is not going to suit everyone. 

And I must admit, I completely agree with him. And the reason for this is genetic polymorphisms, particularly of the CB1 receptor. So truth be told, what that means basically, is that not everyone's receptors, or enzymes, or metabolic pathways are going to work the same. And as such, cannabis will affect them all differently. 

I mean, we've all met one person, haven't we, that said they tried cannabis, and it just made them feel ill or sick, and it wasn't for them. And this is probably because of an example of this polymorphism, which is very common in nature, you know? It's related to biodiversity, to genetic variation and adaptation. 

So not all of our bodies are going to be… we're not all going to have the classic cannabinoid receptor expression that others might have, and therefore cannabis is not going to work for everyone. So, that's a really important caveat that needs to be made clear straightaway.

The second one is that specific cannabis strain selection is absolutely key in getting therapeutic effect, okay? So, limiting patients to just really small amounts of available strains, or even small amounts of isolated active constituents, in my opinion, is going to limit therapeutic potential. 

So we need to actively encourage, and continue to encourage selective breeding programs that are actually going on worldwide, particularly in places like Northern California and Amsterdam, where they're selectively breeding different chemical constituents into the plants for different therapeutic applications. 

And then lastly, which is kind of tying into what we were just talking about when it comes to medical-grade cannabis, is that there is no point having this discussion unless you can actually get patients high-quality cannabis.

Andrew: Yeah.

Justin: So quality control, quality assurance are incredibly important to therapeutic reproducibility so that that patient can go back every time, get the same strain that they like, that is going to give them continued reduction in their chemotherapy nausea, as a side effect, or is going to be able to help them sleep, or whatever it might be. 

And if we're talking about different products, things like cannabis oil, which we haven't even touched on today, but it's incredibly important to make sure from a quality control and quality assurance perspective that we can actually analyse not only for all the different active constituents and their ratios and profiles, but that the solvent residues that they use - because they do use different solvents, like anything from naphtha to isopropyl alcohol to, hexane and stuff like that, you know, which could be quite toxic - and we want to be able to make sure that all of that solvent residue is gone. 

And so I think they're really one of the three most important caveats, it's not for everyone, strain selection is key based on therapeutic applications, and quality control has to be brought in. And at least both the Greens and the Liberals are moving towards setting up legislation that will at least address quality control and quality assurance.

And again, the thing that I'm mostly concerned about which none of them are really tackling at the moment, is what about now? You know, what about now? What about the patients that are out there now, why can't we start to consider them? 

You know, a lot of groups are starting to push for a federal or state moratorium on people that actually have valid medical reasons to… The thing that upsets me so much, Andrew, is that many of these policymakers have never seen a child have 40 focal seizures a day. Many of these policymakers have never seen the absolute, the muscle-wasting, and pain and suffering that patients are suffering from side effects of chemotherapy, you know? They can't keep any food down, and they're suffering, you know? 

This really boils down to, in my opinion, it is a matter of compassion, you know, and it's a matter of perspective. We really need to put some perspective on this discussion, and we need to start thinking in a community of Australians, there's only, what, 23 million of us, we need to look at each other with a little bit of compassion, and understand that if there is something out there now that actually assists these people in improving their quality of life or what little time they have left, this needs to be a matter of great importance for legislators to consider right now.

Andrew: Absolutely hear, hear. Couldn't agree with you more, Justin. Well said. 

So we are going to do another podcast, and I think next time we'll delve into the phytochemistry, the pharmacognosy, that entourage effect. And we'll delve also into the other constituents of cannabis, the terpenes, etc., and all of their effect on the endocannabinoid system, which again, will be five hours long.

Justin: Look, just in finishing, I just want to thank you so much for the opportunity to be able to speak about this. And as you said, this is a contentious issue, and by no means should I be considered an expert in this field. There are so many people out there that just have so much more experience, and I literally feel like a novice when it comes to it. 

But huge kudos to all of the people that aren't even in the scientific community that are still pushing patient advocacy and things like that, the Lucy Haslams, the Lanai Carters, the parents of sufferers that are out there doing it, because they're the ones that have brought this to the public. 

But thanks so much for giving me the opportunity to speak about this with your listeners, and to even have the opportunity to go into a little bit more science in our second podcast. But I'm very privileged, and thanks once again.

Andrew: And that, again, is one of the great things about you, Justin, that is your humbleness. And all of our listeners will agree with me...or agree with me and disagree with you, that you are indeed an expert in the compassionate use of cannabis. So, I thank you for joining us on FX Medicine.

Justin: Thank you so much. And I look forward to speaking with you again.

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


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Justin Sinclair

Justin has been involved in exploring herbal medicines from both a scientific and traditional perspective for over 20 years. He received his Bachelor of Health Science in Naturopathy from the University of New England in 2002 and his Master of Herbal Medicines from Sydney University's faculty of Pharmacy in 2004. 

He has worked as a technical consultant to the CAM industry since 2006 and worked in degree level education since 2007 teaching a wide array of subjects, from anatomy, physiology, clinical pathology and integrated pharmacology to modality specific subjects such as pharmacognosy & phytochemistry, botany and advanced herbal therapeutics.

He has been active in various professional associations, including working as an Executive Director, Board Member Advisory Committee member and Examiner for the National Herbalists Associations of Australia, and currently sits on the Scientific Advisory Board for United in Compassion.

He has published several chapters in leading naturopathic textbooks and articles in peer-reviewed journals on the topics of pain management, herbal medicine and herb/drug interactions. His current clinical and research interests include medicinal cannabis, the endocannabinoid system, plant pharmacology for pain, inflammation, physiological adaptation and immunomodulation.

Visit Justin's website here.