Prescribing medicinal cannabis

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Welcome to the Australian Prescriber podcast. My name is Ashlea Broomfield, and I'm here with Associate Professor Jonathon Arnold, who's a pharmacologist in medicinal cannabis and cannabinoids, and Dr Tamara Nation, who's a GP with a special interest in integrative medicine and medicinal cannabis. Welcome to the podcast.

JA: Thanks for having me.

TN: Hi.

Tamara, could you share with the listeners why you were interested in writing an article for Australian Prescriber on medicinal cannabis?

TN: That's a great question, Ashlea. I was approached by Jonathon and Ian following the recent Senate inquiry into medicinal cannabis, and access to patients. And this was an area of great popularity and concern brought to the Australian parliament, and when Jonathon and Iain asked me whether I would like to be a GP voice for the article, I jumped at the opportunity because it's such an important issue at this point in time.

And what do you see is important about the issue?

TN: So, as outlined in the article, there are many areas which are a concern regarding patient barriers and access to medicinal cannabis, and one of the foremost issues is the lack of education, the issues regarding cost, the issues regarding the stigma associated with the medication. Also, the individual issue around the distinction between medicinal cannabis and black market marijuana.

And Jonathon, what were your interest reasons?

JA: We're interested in writing this article because as part of the Lambert Initiative for Cannabinoid Therapeutics, which is a philanthropic-funded research initiative at the University of Sydney, we conducted some surveys of GPs and they had reported that they did feel quite uneducated about medicinal cannabis in Australia. They were unsure what products are available, what conditions you could use it to treat amongst other things. So, we thought it would be really good to write this article to help doctors in making decisions around medicinal cannabis when their patients are approaching them, but also to understand the regulatory framework as it exists in Australia, which is not always so straightforward.

So, I'm interested to know a little bit more about the types of cannabis that are available in medicinal cannabis form.

JA: Yep. So, in Australia, there's only one registered cannabis-based medicine called Sativex, or the nabiximols they're otherwise known as. So, this is the only one registered on the ARTG, or the Australian Register of Therapeutic Goods. At the moment, they're looking at registering another product called Epidiolex, which is a highly purified form of cannabidiol, which is another phytocannabinoid, and that's for treating intractable epilepsies, and it's already approved by the FDA in the US and the EMA in Europe. But apart from those two products, all other cannabis-based medicines are unregistered medicines, and they need to be accessed via the Special Access Scheme Category B or via the authorised prescriber schemes. Now there's around 100 different cannabis-based medicine products that are available as unregistered medicines at present. Most of them are all oils or capsules that are taken orally. There is also cannabis flower that's available.

The products generally contain varying ratios of THC, which is the main psychoactive constituent in cannabis here, delta-9-tetrahydrocannabinol, or CBD (cannabidiol), which is a non-psychoactive constituent. So, you'll see highly purified CBD-dominant products. You'll see THC-dominant products, but then there's also different shades of grey with 1:1, 10:1, 20:1 ratios of CBD to THC products.

In the article, you spoke a little bit about some of the prohibitive factors or some of the downsides of medicinal cannabis, including cost, quality, and also side effects and effect on driving. Tamara, could you walk us through some of those?

TN: I think taking a step back from that, as Jonathon described, there's a great variety in terms of the unregistered formulations available on the market. So, one of the key considerations, if you're a medicinal cannabis prescriber, is the formulation that you choose needs to be specific to your individual patient, and the side effect profile or the therapeutic efficacy and the therapeutic outcome will also very much depend on an individual patient's genetic factors, their cytochrome P450 system, their metabolism, as well as the other pharmacotherapy that they may currently be on. So, I think in the space of medicinal cannabis, yes, we can have generalised statements regarding side effects. However, you have to bear in mind the type of formulation that you're using, be it CBD, be it THC, and the other terpenes and lesser known cannabinoids in the formulation, which will very much determine an individual's response. So specifically, Ashlea, to kind of just as a blanket outline some of the common side effects, which are usually ascribed to the THC in the product, there are things like dry mouth, there are things like hallucinations, dizziness, memory impairment, there can be nausea, vomiting, changes in bowel function and prolonged high-dose THC use can lead to a cannabis use disorder. It can also have effects on long-term function. So, that's a generalised statement. However, each individual patient will manifest their own response to therapy depending on the dose and depending on the formulation.

And you highlighted some of the issues in relation to education, and I guess this is where some of the controversy lies, in that when you look at the RACGP statement, they say that while there are significant interests in the use of the products for therapy, we need more research into the safety and efficacy on the use of medicinal cannabis products in Australia. That we need education for the general public and medical practitioners that should reflect the state of knowledge and contextualise the use of products as a last-resort medication for a specific category of illnesses that should only be prescribed in rare circumstances after stringent legislative criteria are satisfied. In this environment, why would someone choose to seek out education and upskill and prescribe when it's not yet widely recognised as an acceptable form of therapy? A lot of doctors are saying, "Well, I'm happy to wait for more evidence to come out." What would be your response to that?

TN: So in terms of, for myself as a general practitioner, agree. I've been prescribing now for more than three years, and it certainly wasn't on my radar as something to include in my therapeutic toolkit. However, I did have a patient who saw me in my general practice who wanted to access medicinal cannabis for cance- related pain, and I had the opportunity to undertake an educational module regarding medicinal cannabis at the National Institute of Integrative Medicine, which is where I'm based, and this then enabled me to commence prescription. So, the reason why I went the next step was because of the patient who requested access from me, and with regards to ensuring that I provided best-quality and high-quality medicine, I was very clear and transparent with my patient that this was a therapeutic trial. This was a journey that we were going on together. Not all the side effects and responses were fully known to us. However, I would be monitoring them carefully along the way.

I would choose the best product for their condition from the available evidence, and certainly those key criteria need to be fulfilled for the Special Access Scheme permits. You need to show evidence that you've trialled or considered other first- and second-line therapies. You need to have shown that you've sought expert opinion where required and you need to ensure that you've also ruled out any significant contraindications like unstable cardiovascular disease. So, I did undertake all those checks and balances, and it was driven by my patient who wanted to access this as a therapy for their pain.

JA: So, undoubtedly, more evidence is needed to help practitioners work out the place of cannabis-based medicines use for their patients. But there is quite a lot of existing evidence that you can call upon. For example, in 2017, the National Academy of Science, Engineering and Medicine in the US put together a group of experts who systematically reviewed the evidence on the use of cannabis-based medicines, and what they concluded based on their consensus statement was that there is conclusive and substantial evidence for cannabis-based medicines in the treatment of chronic pain, spasticity associated with multiple sclerosis and also for chemotherapy-induced nausea and vomiting. Now there's been a lot of trials that have been run since then. One of the other major developments where there is pretty good evidence now is the use of cannabidiol (CBD), which is non-intoxicating in the treatment of childhood epilepsies. So, there've been a number of phase III trials now that have been conducted with CBD in the treatment of dry eye syndrome, Lennox-Gastaut syndrome, and also more recently in tuberous sclerosis complex, and in all of those trials, there was a positive outcome.

Now this has led to the FDA and EMA, the big regulatory bodies in the US and Europe, to approve CBD in the form of Epidiolex for the treatment of these conditions. Now, beyond that, yes, no doubt, there's a lot more evidence that is required. There’s smaller trials that show that there might be some efficacy in sleep, fibromyalgia, Tourette syndrome, social anxiety, PTSD, but we do require larger randomised placebo-controlled trials. These trials are coming. At the Lambert Initiative, that's one of the things that we're trying to achieve is improve the evidence through this clinical research.

When we consider that we know after many years of attempting to use opiates to manage chronic, non-cancer pain, that the utility in that context is very limited, is there any more evidence for cannabinoids or medicinal cannabis in the process?

TN: With regards to prescribing medicinal cannabis, as opposed to opioids in patients who suffer from chronic pain, agreed, opioids are no longer first, or second, or even third-line for the management of chronic pain because of the significant side effect profile regarding dependence and also overdose. The key advantage of medicinal cannabis over opioid pharmacotherapy is the reduced risk of respiratory depression and studies, which have been done, which are also available freely on the government website, in the animal models, because it's unethical to undertake this in humans, show that doses between 40 mg/kg to 130 mg/kg are required for dose toxicity. So, it would be extraordinarily rare to cause overdose from cardiovascular respiratory arrest and complications, henceforth the side effect profile is much safer. So, for chronic, complex, resistant pain, it is a reasonable therapeutic option regarding safety profile.

And in regards to the quality of the actual products that we can look into prescribing, are there any concerns regarding the regulation of the products?

TN: So, if you are considering utilising medicine or cannabis in your armamentarium, it would be extraordinarily important to know the providers of your product. As Jonathon said earlier, a lot of the medicinal cannabis products are unregistered. So, it's important that you undertake your own due diligence. Request from the companies their certificate of analysis so you know exactly the nitty gritty of what's inside the product that you're going to prescribe for your patient.

JA: I would just add also that there is some legislation in place, which is a minimum standard for production of medicinal cannabis in Australia, it's called TGO 93. This requires the companies to declare that they've looked at their products for their composition, and they can show certificates of analysis that have some stability data around the products, and also that they can confirm that these products don't contain any heavy metals, microbes, fungus, pesticides, etc. So, there are a few things in place that try to curb any problems with some of the products that are on the market, but of course, I agree with Tamara. You need to do your own due diligence and ensure that you have this information.

In the article you mentioned that a lot of people are using recreational cannabis as a self-prescribing measure. Is use of recreational cannabis a reason not to prescribe medicinal cannabis therapeutically?

TN: I think that's a really good point that you raise. I think we really, as a medical community, need to make the distinction between recreational cannabis and medicinal cannabis. So, when we think about medicinal cannabis, the focus needs to be on the reason why we're going to utilise it in our treatment tool kit. The risk of a patient who has a tendency to develop an addiction or a use disorder needs to be assessed outside of the indication of why we would treat in the first place. So, tick, is this a condition that you would think about medicinal cannabis as a therapeutic tool? Yes or no. Second question, is this patient at risk of developing a use disorder? So, that is a relative contraindication, and if you speak to addiction specialists, they'll also have their opinion in this space. So, at current time, the best tool that we can use to assess whether a patient is at risk of developing a use disorder is the opioid use disorder risk tool, and if you are concerned, then this would be reasonable to run through with your patient.

And the key elements of this tool are things like past history of sexual or physical abuse, a past history of other illicit drug use disorders, a past history of mental health problems, and if any red flags are raised, then it would be reasonable to get a second opinion. It would be reasonable also to set in place certain screening tools in the way that you prescribe. It may be that you discuss with your patient a urinary drug screen from the outset. It may be that you have a cannabis contract with your patients similar to an opioid contract, but ultimately, it will be your clinical judgment with regards to which patients you prescribe this for.

If after listening to this episode, prescribers out there are more interested in finding out how they might go about educating themselves in regards to how they could start prescribing medicinal cannabis, and whether that's something they're interested in, what are some suggested ways that they could go about that?

There's a plethora of courses, and a lot of them have RACGP CPD points attached to them. Multiple institutes are offering medicinal cannabis education. Most of the medicinal cannabis companies also run regular workshops and webinars that can be accessed. Typically, there will be an educational event every six to eight weeks in this space, and as Jonathon said earlier, there's a significant amount available in the literature to access as well.

If listeners would like to know more about the different pathways of applications in each state, feel free to look at the article in this edition of Australian Prescriber. Is there anything else you wanted to add?

JA: I guess, there's just the ongoing challenge of a lot of people using cannabis for medicinal purposes, but through illegal channels. So, a recent survey came out by the National Drug Strategy Household survey, where they surveyed a significant population of Australia, and what they'd worked out was that there was probably around 600,000 people that could be using cannabis for medicinal purposes, that the vast majority of those are using it illegally still. Only 3.9% of people are actually using it through legal pathways. So I would say there's an ongoing challenge there really, to transition people from the illegal access through to legal access pathways, and the great benefit for the patients would be that at least with even the unregistered medications, there are some standards that need to be adhered to. You can be pretty sure it's not going to contain heavy metals and pesticides, which could occur with illegal cannabis supply, and also with illegal cannabis supply, most of it is rich in THC. It won't have as high concentrations of CBD, and CBD appears to have some benefits in reducing anxiety and antipsychotic effects, which could be beneficial in a cannabis preparation.

Thank you for joining us on the Australian Prescriber podcast.

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The views of the guests and the hosts of this episode are their own and do not reflect Australian Prescriber or NPS MedicineWise. My name is Ashlea Broomfield and thank you for joining us.