In the 2016 National Drug Strategy Household Survey 1.3million Australians (6.3%) over the age of 14 reported having ever used methamphetamine, with 1.4% reporting recent use, within the previous twelve months. Worse still, of meth/amphetamine users, "ice" is fast becoming the preferred form of the drug, with increases in Australia from 22% to 57% in just 6 years. [1,2] Ice addiction has been a growing problem in Australia both for users and the wider community impacted by the social and behavioural aspects brought about by the use of the drug.
Today we're talking with Associate Professor Olivia Dean who is part of the team conducting a world first study to determine if N-Acetyl-cysteine (NAC) can reduce the craving for ice and ultimately, help them overcome their addiction. Known as the N-ICE trial, it's taking place right now in centres in Wollongong, Geelong and Melbourne. Olivia shares why they're exploring NAC, how it's being administered and what they hope to achieve with the study.
Covered in this episode
[00:44] Welcoming A/Prof. Olivia Dean
[01:43] What are Impact Trials?
[02:38] Repurposing medications for psychiatric use
[04:12] Some of the challenges for nutraceutical research
[11:02] What is the N-ICE Trial?
[14:02] Physiological changes in methamphetamine addiction
[18:05] Can receptor function be restored?
[20:26] The addictive nature of Ice.
[21:48] NAC pharmacodynamics?
[23:24] Mitigating other effects of Ice
[24:27] Compliance with NAC
[27:10] Dosage and delivery of NAC in the N-ICE trial
[28:58] Recruitment and roll out of the N-ICE trial
[34:06] Where to find further information on N-ICE trial?
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us on the line today is Associate Professor, Olivia Dean, who is currently director of impact trials within the Centre for Innovations in Mental and Physical Health and Clinical Treatments Impact. And an RD right NHMRC biomedical career development fellow at Deakin Uni. There's a mouthful. She holds honorary appointments with the Florey Institute of Neuroscience and Mental Health, University of Melbourne and Barwon Health.
Olivia has established a solid track record with over 100 publications and several successful grants totalling over $8 million. Dr. Dean is committed to providing better treatment outcomes for people with mental disorders and is actively involved in ensuring her research reaches community forums and outcomes and are directly translated into clinical practice. Welcome to FX Medicine, Olivia Dean. How are you?
Olivia: Good. Thanks very much for having me.
Andrew: It is my honour. When I first heard about this trial that we will be talking about today called the N-ICE Trial, it's not nice. But let's first go into a little bit of your work. That was a heck of a mouthful. What do you do at Impact Trials?
Olivia: Sure. Unfortunately, most of the things we do need a lot of explanation as they come with quite long titles. It's the nature of research, I think. We like to be all-inclusive.
Olivia: But the crux of what we're doing, really is about looking for new therapies for people with psychiatric disorders. Because we know that the current therapies while effective, they often leave a short fall in recovery. So we're looking at ways that we can enhance current therapies by adding in new things, especially around nutraceuticals and repurposing medications to improve outcomes for people with psychiatric disorders.
Andrew: Let's investigate that ‘repurposing of medications.’ You know, when you get a, you know, an authorised use for a medicine, for a pharmacological agent, it takes a heck of a lot of off-label use first and then the ground swell of research starts to take place. But there's a long lag time between when it's used off-label for something, then it gains success, then it gains some research notoriety and then it's accepted by government. How long does that sort of slow wheel of medicine take?
Olivia: Sure. I mean, that process takes years to actually get an agent from discovery into something like the PBS listing, for example.
But our approach actually harnesses a shortcut that I think is beneficial. And so, instead of thinking about it as the long process to actually having an approved agent, we think about it the other way, in that these agents are already approved for some indications, safety and tolerability is well established, and then we can use them for off-label or other indications as you suggest. So, instead of having to start with a potential molecule and then spend millions and millions of dollars developing it and doing pre-clinical and first in humans, trials and all these sorts of things, it takes 15 years to even identify a candidate, we're fast forwarding the whole process by using drugs or medications that are already established and available and seeing if we can reuse some of their mechanisms of action for psychiatric purposes.
Andrew: With regards to nutrients and nutraceuticals, you know, normally... I don't know about, particularly with psychiatry, but certainly with orthodox medicine, there's this skepticism? That that simply doesn't work and the effects are placebo. How do you engage with health professionals to say, "Look, it really does have a research basis and there really is some sort of premise, at least, a proof of concept?"
Olivia: I think, unfortunately, there has been an issue with the quality and the composition of a lot of the nutraceuticals that are available at the moment. There are very few regulations required in terms of having to prove what is in the bottle, is in the bottle. Whereas in medications, obviously, that is regulated quite strongly. When it comes to nutraceuticals, that's not always the case. And so, I think what that's led to is a mistrust between medical clinicians and the nutraceutical world. Because while there may be benefits in some of these nutraceuticals, there are so many agents out there that may be misrepresenting what they're offering that there's a lot of scepticism.
So I think that there's a twofold approach that we can do to change things. The first one is to provide rigorous scientific evidence for nutraceuticals that have been tested and proven to be what they say they are. So, for example, we're running a study looking at a fruit extract and we've done some benchmark testing to at least show that what we believe is going on in this extract is actually in the extract and that we we can then replicate that down the track. And I think really, that's what clinicians are looking for, is replicated science to back up some of these claims.
The other thing I think that's going to be really important is the changes in regulations required by nutraceutical companies to actually meet some of these regulations.
Andrew: With regards to that reproducibility, you know, this is one of the issues, I think, that supplement manufacturers have in putting forward or putting up the money to prove that their vitamin, you know, B3 has an effect on skin cancer, for example. Because, company X does the research, company X puts up the millions and millions of dollars required to get the, you know, phase three multi-centre trials done, and Company Y then says, "Thanks very much. My B3 is the same."
Now, I guess that's a little bit different when you're talking about fruit and herb extracts because you might be able to nuance those to a, you know, an intellectual property, dare I say that word. But how do you cover that sort of thing about patenting?
Olivia: Sure. So from the, I guess, you know, from the drug development side of things, it's been one of the issues that we're having in drug discovery in psychiatry in that there are very few targets available to patent from. So there's a lot of repurposing of analogs and those sorts of things, but really, there is nothing new in the pipeline.
And as you said, if you do the discovery work for a particular indication for something that's generic, then anyone can then go and market that.
Olivia: So it's problematic to get investment into that. But on the flip side, it does mean that if we can show that there's a valid scientific application, then at least translation into clinical practice can be straightforward.
Olivia: So it's sort of a two sides of the coin. We can't make a commercial application here and we can't make money or those sorts of things, but we can at least have an agent that is readily available to everyone. And we as scientists can provide that scientific evidence to back up some of those claims.
So, for me, I'm not as concerned about the lack of commercialisation opportunities because I just want people to be able to get these medications or these nutraceuticals.
Andrew: Yeah. Do you think there's a reasonable call then for scientific institutions to, you know, ask, implore, for funding for not one, but multiple, you know, supplement manufacturers to say, put into a pool which you can draw off and we can then, you know, benefit all of you if you want?
Olivia: Absolutely. I think that would be ideal and I would be more than happy to be involved in discussions around that. I think what it will ultimately come back to though is what does the company get back if they're going to invest into a group pool?
Olivia: Because of things like IP and patents and those sorts of things. And the other thing is, is that unfortunately, there is little incentive for some companies to invest because they can market their product without scientific evidence.
So, if you have a situation where you can push a product for a particular indication without having to do millions and millions of dollars of R&D, then you're going to probably do that.
Andrew: Yeah. So when you say without scientific evidence, though, I mean, companies are required to have a, you know, at least a backup of science to say, "It's useful for this." You can't just say it's useful for that when it's not. That, you know, for instance, you know, vitamin B3 for nerve health or something. There's got to be some background research on that, but you can't then claim that it's been proven to cure, you know, X, Y, Z condition because you haven't done the millions and millions of dollars for the licensing of that. Is that what you're saying?
Olivia: Yeah. So that's it. So, I think a lot of the ways around that issue at the moment, at least from the company perspective, would be to claim things that you can't prove. Like, this drug will improve wellness. Or this drug will improve wellbeing. Wellbeing is a really popular one at the moment because you don't actually need to provide claims evidence.
Andrew: Isn't that dictated how the TGA, though?
Olivia: That is absolutely dictated by the TGA but there's a gray area between what's considered a proper health supplement and what's considered a food supplement.
Olivia: And so, I don't think we've got enough time to get into the complexities, though.
Andrew: So despite the TGA being really the premiere legislative body for the quality of supplements, there's still a long way to go?
Olivia: Absolutely. And then, there are limitations on the things that they can regulate, and obviously, if you're, if a company is making specific claims, they need to be backed up by evidence and the TGA will look into that.
Andrew: Yeah. Cool. So let's look at this trial that we're talking about today, the N-ICE Trial. What's the trial acronym for and where did it first start from?
Olivia: Sure. So N-ICE is N, ICE, which is actually a amalgamation of N-acetyl-cysteine for ice.
N-acetyl-cysteine is an amino acid and a medication that's been used for decades. It's most commonly known as the antidote to paracetamol overdose. So, if you take too much paracetamol you go into emergency and they will give you N-acetyl-cysteine or NAC, to fix you.
The pathways that it works on in the liver in terms of paracetamol overdose are involved in what we think is going on in addiction, but there's actually a series of other mechanisms that NAC actually has, that we think might be useful for methamphetamine or ice addiction.
Andrew: Right. So, you're talking there, obviously, a reward system, which is commonly the issue with, you know, the addiction to ice, but also an as an antioxidant. Is that right?
Olivia: That's it. So, if we take a step right back to where this story first started, NAC's been used for some time in our hands as an adjunctive therapy for psychiatric disorders. We found it to be beneficial for predominant...for effective disorders, in schizophrenia. And in parallel with our research line, there were several groups around the world looking at it for its potential for addiction applications because of the mechanisms around glutamate, which I'll get to.
So, what we did was, we were working with NAC for a variety of reasons. There was a lot of this evidence coming out of the addictions world, as well as pre-clinical evidence showing that NAC works on not only as an antioxidant, which we're well aware of, but has significant effects on the glutamatergic pathways. And that in pre-clinical models, if you interrupted addiction models with NAC, you could see changes in glutamatergic pathways that would lead to reductions in craving.
And so, with putting all of that together. Rebecca McKetin from Curtin University approached us and she has a longstanding history in substance use research, came to us and said, "I think this would be really useful as a treatment for methamphetamine or ice dependence. Would you be interested in running a study?"
And that's really where the study came from. And from then, we have received NHMRC; funding to actually conduct all the clinical trial, and in parallel, we've being keeping an eye on the pre-clinical literature to find more and more ways that we can support what we think is going on clinically.
So, coming back to the reward pathway, the theory is, in addiction, is that there are, that in the case of ice, the methamphetamine changes the glutamate pathways through interactions between dopamine and glutamate and that's because methamphetamine induces floods of dopamine release and this interacts with the glutamatergic pathways, ultimately leading to changes in the reward pathway in the nucleus accumbens.
And what that means is, is that for people who have become dependent on ice, their brains have changed in such a way that they crave and require the methamphetamine to dampen the receptors screaming out for the, sorry, screaming out for the need for the drug and then dampening the craving pathways.
So, coming back full circle, if we can give people NAC, we might be able to reset the glutamatergic pathways and this may, in turn, reset their craving desires and that will reset their behaviour and hopefully, that will get them of ice.
Andrew: Yeah. Can I clear something in my mind? When you have something like a drug, like ice, flooding the brain, the dopaminergic receptors in the nucleus accumbens being affected, are we talking about the drug causing damage to the receptors so therefore they don't work, so therefore the subsequent release of dopamine by, you know, endogenous means, just doesn't have any effect? Or are you talking about an up regulation of receptors so that the low amounts that the normally body produces just aren't enough?
Olivia: So, there's a twofold effect that's going on here. The increase in dopamine release that is caused by methamphetamine use, which is the part that we're looking for, to get high. It will cause a damage to dopamine receptors over time. Because they're over worked effectively.
Andrew: Yep, yep.
Olivia: And this causes two problems. It up-regulates the amount of dopamine receptors that may be available, so there's more dopamine receptors. And it also creates a sensitivity in those receptors.
So, you've got a situation where dopamine's coming into the system, it's excessive dopamine, which is great in terms of getting high, but the system has to compensate for that in several ways. And it does that by up regulation of receptors and changes in the receptor profile.
Olivia: And what that ultimately leads to is downstream changes in systems biology. So, it's not just at the receptor face, this actually causes negative feedback loops with things like the glutamate system that's expecting normal dopamine transmission to tell it how to regulate things like craving and those sorts of things. And when that system and those receptors are so far changed from their usual regulatory pattern, the normal physiology can no longer occur. And that's why you get this shift. And there's a shift not only in the dopamine receptors in the frontal cortex and in the nucleus accumbens, but these changes in the glutamatergic pathways seem to be fixed.
So, even when you take away the drug, those changes remain over time and they need to be reset and that's why there's such high level of relapse in people that have come off of a drug, any drug, but including methamphetamine. Their withdrawal of the drug doesn't instantly reset the system. And so, there's a time and a change factor that needs to happen to try and reset that system. And unfortunately, that can take years and that's why people have such high rates of relapse.
Olivia: Absolutely. So, there are... And the other thing too, is just that addiction isn't just a biological activity, you know?
Andrew: Yeah, yep.
Olivia: It's a combination of a biological activity and a behavioural one. So, I think if you withdraw a drug, there are immediate benefits that you're going to see in terms of both biology and behaviour, but there are changes that you can expect that will take quite a long time too.
So, for instance, you might see that in the early stages of methamphetamine withdrawal, obviously, after they've gone through the initial withdrawal, that people might feel that their irritability and their paranoia might be reduced immediately because you've actually withdrawn the drug. But their cravings and their willingness to want to keep taking the drug will take some time to change. Because those are more downstream pathways.
Andrew: Yeah. And this goes back to social support and why they had that need to try that drug in the first place. Yeah?
Olivia: Absolutely. And that's one of the key points that we're making about the N-ICE Trial and NAC, in particular. Is that at the moment, there is no substitution for methamphetamine as there is in other indications. There is some work in using dexamphetamine, but that's been problematic in itself and it's not from what I've been told by clinicians, a ideal option.
So, having a medication that people could take immediately when they feel like they want to stop methamphetamine is, I think, really important. But it's always going to be part of a bigger picture of social support, behavioural or lifestyle changes, and a revision of where you wanted to be in your life and how you might change that. And it sounds very simple, but obviously, it's very complicated.
Andrew: Oh no, gawd. Absolutely.
Olivia: And as you touched on, the complexities of people's lives that drives them to drug use generally don't just magically go away because they've decided to change their drug use.
Andrew: Yeah. Can I ask about ice addiction and the realities of how quickly it becomes addictive? I have been told, I am not an expert in this whatsoever. I have been told that it's basically one hit and you're now it's slave. Is that actually true or is that more myth?
Olivia: Look, I think it's not that black and white, and I wouldn't want to commit to an answer that says, "Oh, no, absolutely, not," or, "Oh, no, absolutely, yes." I don't think it's that straightforward. What I can say, though, is that we have seen, at least, in the literature of that one dose will make brain changes.
Olivia: So, if you take one dose of methamphetamine, you can see that it will actually have a long-term consequence on your brain. Whether or not that directly leads to an addiction, you just can't make that connection.
Andrew: Got you.
Olivia: It's just not that straightforward.
Andrew: Yeah. Because of the whole purpose for what they took it for, the social support mechanisms around them. And so, there's a whole web surrounding that addictive behaviour.
Olivia: And also, just the inherent biology of the individual. So, some people have receptor profiles that can tolerate higher levels of drug use before they become significantly altered than others. And that's just a factor of genetics and biology, you know? You can't pick that.
Olivia: Yes, is the short answer. So, we know that N-acetyl-cysteine or NAC directly interacts with the glutamatergic levels, so like levels of glutamate in the brain through the cysteine glutamate exchanger. We also know that NAC has direct effects on dopaminergic transmission and also has a role through its antioxidant capacity in things like mopping up quinones, which also has an effect on dopaminergic transmission.
In terms of a direct synergy and how we're going to actually look at, for instance, is NAC going to block dopaminergic receptors so that you're not going to get a high? No, that's not what we're postulating. What we are postulating is that NAC will work to change that cysteine glutamate exchanger and that will regulate the glutamate levels, which will hopefully then regulate the system and have a downstream effect on craving.
The trial itself is actually looking at decreased use. So, it's not pinning everything on the fact that people have to stop, it's about decreasing their cravings and hopefully, decreasing their use.
Olivia: Sure. So I can't really comment on hypothermia although there has been some animal work that's shown that there is an interaction there between NAC and hypothermia. But one of the really interesting things that I think might be useful for people with methamphetamine taking NAC, is that we've shown that it may actually improve symptoms for people with schizophrenia.
Olivia: And so, there may be an interaction between the psychotic effects of methamphetamine and the anti... I don't want to say anti-psychotic effects because we haven't actually shown that, but there may be some control of schizophrenia-like symptoms in people who are taking methamphetamine.
Andrew: Right. Well, certainly useful, anyway. I mean, given that, you know, an at-risk population, I mean, that's certainly worthwhile.
Olivia: Absolutely. And it has a relatively low side effect profile, so I think that makes it easy to tolerate and easy to take, and that's going to increase the chances of someone actually taking it.
Andrew: Well, let's go into that. Compliance issues. You know, you've got somebody addicted to methamphetamines. How do you... I can't say the word ensure, how do you improve compliance issues given that N-acetyl-cysteine does not taste like a fruit jello lolly?
Olivia: So, I think there's a lot of misconception and definitely a high amount of stigma about methamphetamine users. People don't really understand that a lot of users actually don't want to be using the drug anymore and that they falling into a trap where they really can't get out.
And what we're finding, at least, in my experience recruiting for this trial, is that the people that are coming to us generally fall into two categories, and this is very much a generalisation. They've either tried what's out there, which is detox and rehab, and they found that that wasn't sufficient to actually make the changes that they needed to make. Or, they've wanting to go into detox or rehab and they're finding the waitlists are too long.
Andrew: Oh, right.
Olivia: Really, what I hope that this will provide is a stop gap. So, NAC will be provided to people basically as soon as they decide that they want to get off meth, and then all of the other things will fall into place as well. You know, that this wouldn't be a standalone treatment, but it would provide an immediate option for people that wanted to stop taking methamphetamine. Because I think that really is important, that when you reach the point where you want to stop, you can't wait six weeks to get on to some waiting list and then finally get into somewhere.
Olivia: You need to have an action plan that day, in that moment.
Andrew: That's right.
Olivia: And I think NAC will be really useful. If it sounds to be positive, it'll be really useful in that respect.
Olivia: Because people do want to get off the drug. They do want that, you know, they don't want to be running around psychotic, and having an option that will be immediate, I think, will be really useful.
Andrew: Absolutely. So it really is like a rescue medication, as you first mentioned, with paracetamol overdose. Something that you can use now and can have an effect quickly as a...let's call it a band-aid, until they can get into the detox programs.
Olivia: Yeah. That will be how I would I would see it would work over the long term. And obviously, hopefully, the time to get into rehabilitation programs is shortened. But by the time they get there, the NAC has actually started to take effect. So, they're going into their programs with a headstart on changing their craving pathways.
Andrew: Got you.
Olivia: Which I think hopefully, we'll actually reduce the amount of relapse further down the track.
Olivia: Yup. So, this study is using, from memory, 2,800 milligrams a day, and that's provided as capsules. And people basically have had no issue with tolerating it or with taking it, the normal size capsule. There's nothing for the unusual about the intervention.
And we've found that people, generally, who are on the study have completed the 12 weeks of the trial because they have a commitment to getting off the methamphetamine. So, it's actually been fairly good in terms of participant retention and definitely, very high and number of people wanting to come in. So, recruitment has been really quite rapid because there's such a high need out there.
Andrew: That was one of my questions. Like, I had prejudged this group of patients being sort of reticent about enrolling into a trial because of the legal implications of, you know, being found out and all that sort of thing.
But you're saying the compliance is actually really high, the engagement with these patients is something that they actually want to do. So, it's a total... I'm totally and utterly misjudged this group of patients.
Olivia: Yeah. And I think people do misjudge ice users, generally. And I think that's got a lot to do with the media's portrayal of them. Unfortunately, the predominance of the people you see in the media are psychotic and violent. And that is absolutely the case for a lot of methamphetamine users, but it's not the case for all. And it's my, by no means, the general case.
Olivia: No, recruitment's still ongoing and we are looking for more recruits. We're recruiting out of three centres, one in Wollongong, one Melbourne, and one in Geelong. We plan to recruit until approximately the end of the year where we're hoping to have everyone we need involved.
The study is placebo-controlled, so we've got 50% of the participants taking a placebo and 50% taking the active. But everyone gets a little flyer at the end to say where they can purchase NAC if they want to do that themselves later, which is something I think, again, is really useful about re-purposing medications, is that these are readily available so people can go and get them themselves.
Andrew: Okay. I know I'm sort of read digging up a TGA issue, but currently, N-acetyl-cysteine in Australia isn't in capsules, it's in powder, at least, in the supplemental form. Are you talking about a drug or pharmaceutical availability?
Olivia: So there is... So NAC falls into a very strange category.
Andrew: I know.
Olivia: One gram or less it's considered a food supplement, at one gram or more is considered a medicine.
Andrew: Got you.
Olivia: So, what we've found is the compounding pharmacists are quite compounded, and they'll compound it, generally, at 1000 milligrams or less a capsule size, so that that fits quite well. They don't need to worry about regulatory issues there. Even though they're compounding pharmacists, which would mean that would be fine.
We have some nutraceutical companies that are selling it at doses less than one gram, so therefore, it's being sold as a health supplement and people can get it that way. And you can also import it for personal use over the internet. So, people are getting it...
Andrew: Which a whole issue of quality that we have discussed previously.
Andrew: So three centres. What about regional application or regional participants in the trial?
Olivia: Well, I would consider Wollongong sort of regional.
Andrew: Sort of. They'd hate you saying that.
Olivia: Well, I was going to say and Geelong, and I'm in Geelong, so there you go.
Andrew: All right. What about rolling this out to more regional areas though? I mean, there's a huge issue in the country.
Olivia: Absolutely. And I think, again, it comes back to the potential that this might have to actually make significant change. Because regional areas do have a paucity of services. They do have long waiting lists and these sorts of things. If we can get NAC them straight away, again, it's that stop gap. It's trying to put the bandaid on and maybe that'll be enough to at least get people to be able to, you know, get by, until they can actually get into formal drug treatment.
Or ultimately, that there may be some synergistic approach where this drug is included in a online or a Telehealth, or something similar program where they you're not required to actually physically go to a centre to have rehabilitation, but that can be offered to you online.
Olivia: To me, that would be ideal.
Olivia: That's definitely a pipe dream and nothing that I'm involved with at the moment in organizing.
Andrew: Yeah. There's a lot of health reshuffling that needs to happen before then. I mean, you know, mental health is an area which is just in a sorry state of affairs and that's been rather publicly acknowledged. I've seen rather recent issues or examples of that where people just aren't getting the support or care that they require.
You know, I mean, I'm so excited. When I first found out about this, I thought, "Oh, my goodness. This has the potential. It's not proven yet, but it has the potential to affect so many lives in a positive way." And we're not just talking about the people affected either, we're talking about the people that are affected by those who have methamphetamine addictions. It's brilliant.
Olivia: Oh, absolutely. And, you know, I think the stigma around mental illness is changing and I think that will lead to a change in service provision, hopefully.
And I think too, that it sounds really obvious to people in the field, but for too long, mental health was considered so separate to medicine, which just seems so ridiculous now.
So, I think the fact that we've all agreed that the brain is part of the body will make some significant changes in terms of people's thinking around mental health and then hopefully, the resources and the funding around that will increase.
The other thing to note on that too is, unfortunately, when we're talking about stigma, mental health or mental illness still carries a lot of stigma and then addiction is on top of that.
Andrew; Yes, yes. Yeah.
Olivia: So, getting help to people that are often misunderstood and generalised in negative ways, I think, is really important.
Andrew: Absolutely. I yearn for the day when it is no longer said, "It's all in your mind," but it's said, 'It's in your mind and the rest of your body and we'll offer you support for that." Where can we find out more about this for practitioners, and indeed, patients who might be out there listening and, you know, want to enrol in the trial?
Olivia: Sure. So, we have a website. I think you can do Google N-ICE, but it is through the Curtin… it's housed by Curtin University, so I'm sure you can find it through there. We also have, Curtin's put up a Facebook page called N-ICE Trial and I'm available on the Twitters at the @DrOliviaDean handle. So you can contact us through a variety of ways. Otherwise, you can just contact us directly through Impact and we'll be in touch with you there.
Andrew: You are doing brilliant work. Absolutely brilliant work, Olivia. Thank you so much for taking us through the N-ICE Trial today and explaining more about, indeed, dispelling some of the myths regarding those people that may be affected themselves by methamphetamine use and addiction and offering them, hopefully, some secure in the future. Well done.
Olivia: Oh, thanks so much. And I think it's really important that we get the message out there, so hopefully the trial's a success and we can make some changes.
Andrew: Yes, exactly. And we'll put as much information and support material that we can up on the fxmedicine.com.au website. Thanks so much for joining us on FX Medicine today.
Olivia: Thank you.
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook.