For more info on The Lumir Mission Plant-based Medicine for Primary Dysmenorrhoea (Period Pain) Study head here
TRANSCRIPT
Kel: I'm Kel Myers and you're listening to Phoenix Sound.
In today's episode, I'm thrilled to welcome Dr. Kylie O'Brien, Chief Scientific Officer at Cannim Group.
Under her leadership, Cannim is sponsoring the Lumir Mission plant based medicine for primary dysmenorrhea study, conducted by the NICM Health Research Institute.
This study investigates the potential of plant based medicine to alleviate period pain. A condition that many women and girls endure in in silence because it's often dismissed as normal.
Having experienced debilitating periods for decades myself before being diagnosed with endometriosis four years ago, I understand the effect period pain can have on a person's life and how hard it is to find relief.
In the quest to find effective treatment, Dr. Kylie is at the forefront of promoting education and advocacy in her field. And today we'll dive into the scientific endeavors and goals of this crucial research, uncovering what makes this study such a significant leap forward in women's health. Stay with hi Kylie.
So can you give us an overview of the medicinal cannabis for primary dysmenorrhea study and what prompted the research team to explore this specific area?
Dr Kylie O'Brien: Well it’s a longitudinal, prospective, observational study in 65 women who are aged 20 years or over who are suffering from Primary Dysmenorrhea.
And it'll investigate the effectiveness of medicinal cannabis over six months.
So, Primary Dysmenorrhea is period pain which is not associated with any kind of pathology in the pelvis.
So, in this study, participants will have a consultation with a medical doctor and be prescribed the medicinal cannabis products from a project formulary and they'll complete various questionnaires at baseline and then monthly online. So, study's been conducted by the NICM Health Research Institute at Western Sydney University.
So, the, the NICM Health Research Institute, one of the top research institutes for research into plant based medicines, including medicinal cannabis.
So I guess the key aim of the study is to investigate whether medicinal cannabis products as a whole, as well as specific subcategories, which we call chemotypes of products are effective in alleviating pelvic pain associated with Primary dysmenorrhea, as well as some of the other symptoms that you get associated with it.
And I'll just explain those terms.
Chemotype One is a high THC cannabis product.
Chemotype Two is a balanced product where you get similar ratios of the two major phyto cannabinoids, Tetra hydro cannabinol, or THC and cannabidiol or CBD.
And then the Chemotype Three is the high CBD with low THC types of products.
So when you ask about what prompted us to explore this specific area of health, well, I guess it's been a lot of research conducted into different forms of chronic pain. And there's some evidence from systematic reviews that indicates that medicinal cannabis might be able to alleviate at least some forms of chronic pain.
And when I looked into it I found that there haven't been a lot of studies specifically in primary dysmenorrhea.
So there was a large, what they call systematic review of medicinal cannabis use for gynaecological pain and that was 16 studies.
And a subset of, set of that was seven studies, which were seven cross sectional surveys, which investigated whether cannabis to treat gynaecological pain was useful or not.
And in that study, they found that the prevalence of cannabis use was anywhere between 13 and 27 percent across four of those studies.
The rate of pain relief was anywhere between 61 and 95 percent across Six studies.
Kel: Wow. They're huge numbers, aren't they? 61. Can you just say that again? 61 to 90.
Dr Kylie O'Brien: 95%. So the rate of pain relief across the six studies that looked at this found that the rate of pain relief was anywhere between 61 and 95%. And some of the studies, interestingly, also found that medicinal cannabis use was associated with decreased analgesic use, including opioids.
But the thing was, none of those studies were specifically in primary dysmenorrhea.
They were in gynaecological pain due to a number of different things. But none in primary dysmenorrhea.
Then I found another study that was done in Australia.
It was qualitative research. It was like a focus group in 26 women with primary dysmenorrhea this time, and it found that the current treatment strategies like non-steroidal anti-inflammatory drugs and heat and other non-pharmaceutical management didn't provide adequate pain control and there was a dissatisfaction with the current management strategies like over the counter analgesics was a key driver for these particular women wanting to use medicinal cannabis.
So up until then when I first did the literature research, that was largely what I found.
But then recently I found a study had been published in Cannabidiol Isolate, which suggests that it may reduce menstruation related symptoms like anxiety and irritability and stress.
So and of course there's studies in other populations that indicate that medicinal cannabis might be effective for things like anxiety and poor sleep. And so those are often also there -they call them comorbidities as well as the pain in primary dysmenorrhea.
So we've got a few studies that are sort of pointing in the right direction saying well possibly this might work for primary dysmenorrhea but there really is a lack of, of clinical research to be able to guide practitioners into whether you know medicinal cannabis might be a suitable option for women who aren't responding to say orthodox strategies.
And I suppose the other bit of interesting stuff is that when you look in the animal research they have found and other forms of research, cell research, they call that preclinical research, we do know that components of medicinal cannabis have got anti inflammatory actions, as well as analgesic actions, we do know from studies in animal models that THC and a, what they call a synthetic isomer of CBD, as well as agonists, of the cannabinoid receptors in the body can reduce excessive myometrial contractility in animal models.
And that's part of what causes the pain in primary dysmenorrhea is that you get excess contractility of the muscle layer in the uterus.
So, I guess when you look at it, the endocannabinoid system, a lot of people don't understand that we've got this regulatory neuro- and immuno- regulatory system in the body that regulates most bodily systems, if not all of them.
And it's very relevant to primary dysmenorrhea because we have the endocannabinoid system components in the reproductive organs.
So the endocannabinoid system regulates analgesia and pain, stress and emotions, sleep, nausea and vomiting. It regulates so many different things in the body. I've just read out some of the ones that are kind of relevant to primary dysmenorrhea.
And the other thing is that components of medicinal cannabis, can interact with that endocannabinoid system. So when you put all that together, you think, all right, well, there is some rationale for bothering to go into some clinical research, at least some preliminary research, which is what we're doing.
It's a small study in women with primary dysmenorrhea to find out, well, could it be effective or not?
Kel: Yeah, I'd love to come back to the CBD and the THC and the distinction between the two in a minute. But I'll just park that for a second while we just go through the research methodology.
I'm just wondering what the criteria was for selecting participants and how do you ensure that the treatment is suitable given how complex medicinal cannabis is.
Dr Kylie O'Brien: Yeah, well look like any other substance study there are definite inclusion criteria and exclusion criteria for coming into a study.
So some of the inclusion criteria, I won't read them all out, but obviously they've got to have primary dysmenorrhea not secondary dysmenorrhea, so secondary dsymenorrhea is period pain, but it's due to a pathology like endometriosis, for example.
So we're working with primary dysmenorrhea.
The participants have to be 20 years or over and not used cannabis within the last three months.
They've got to be willing to undertake some safety blood tests and be able and willing to complete the study questionnaires sent to them and be obviously willing to give informed consent to be part of the study. And they've got to be willing to use contraception for the duration of the study.
And they're the sort of standard things I guess you'd expect in a clinical study.
And then there's a range of exclusion criteria.
So for example you know, a, a current medical condition, which in the opinion of the study coordinator or the medicinal cannabis doctor who's going to be involved in the study is a contraindication for medicinal cannabis; if they're pregnant or planning to become pregnant during the study duration then they can't come into the study; if they're not willing to use contraception for the duration of the study.
So there's a number of different inclusion and exclusion criteria that if people are interested in looking at, our participating clinic the Natura Healthcare Clinic website has the details for that.
But look, at the end of the day, even if someone was screened and look, they met the inclusion criteria and didn't have any of those exclusion criteria, and they came into the study the first, I guess, step is that they have to have a consultation with a doctor through Natura Healthcare Clinic.
And that doctor will really ultimately decide -are they suitable for treatment with medicinal cannabis or not? And if the doctor says, "I don't think medicinal cannabis is actually suitable for you", for whatever reason, then it's not going to be prescribed and that potential participant wouldn't be able to continue in the study.
So at the end of the day I guess the medical doctor has the last word on whether someone comes into the study.
Kel: Now, just circling back to medicinal cannabis and its role, I think, you know, there's a lot of misinformation and pseudoscience that orbits around medicinal cannabis, as you, you will well know.
Distorting what it is and how it works in the body. Yes. And particularly, I think, when it comes to the distinction between CBD and THC. Yes. Now, for those who are new to the space, like many of us, people are, most of the general public are seeking clarity. I'd love it if you could explain the differences just on a basic level of say high THC versus high CBD formulations.
And also as well, just an additional point, what types of medicinal cannabis products are being used in the study? I'd love to know that too - thank you.
Dr Kylie O'Brien: Two great questions. And look, medicinal cannabis, cannabis has, you know, it has almost 2000 constituents in it.
There's probably now well over 200 what they call phyto cannabinoids.
And they've got many different terpenes.
The terpenes are essential oil like substances that give the plant its characteristic smell, and you've got many other plant nutrients.
So it's not just one thing, but mostly people hear about the two major phyto cannabinoids: tetrahydrocannabinol or THC and cannabidiol or CBD.
But there are other minor phyto cannabinoids as well, and they've got therapeutic actions.
So it's believed that the combination of all these plant nutrients is what helps determine the therapeutic action of different medicinal cannabis products.
So it's not just one thing in other words.
So it's not just CBD and THC. They call that the entourage effect where it's the other plant nutrients are adding to the overall therapeutic effect.
So medicinal cannabis is not one thing. It's not just one product.
And depending on what's in that medicinal cannabis product, that may impact on the therapeutic effect.
So THC and CBD are the two main phytocannabinoids. The main difference, I suppose, is that THC is the only phytocannabinoid that is associated with that potentially euphoric effect that you associate with, you know, for example, the smoking of cannabis recreationally or for adult use.
CBD does not have that potentially euphoric effect.
And I say potentially because it's dose dependent.
So, you know, with THC, if you have a small amount of THC, that's not going to cause that euphoria. If you have a large amount, yes, it could, as well as a whole lot of other perhaps less desirable side effects as well.
I think there's a big misconception that cannabis is one thing and you know, when it's actually not.
So CBD is not addictive. It doesn't havethat potential euphoria like THC can do.
But it's not to say it's not psychoactive because it's anxiolytic which means it can reduce anxiety for example.
So it does have an effect you know on your psyche if you like.
So the two of them, they work in different ways, so THC is what they call a partial agonist, which means it binds with the cannabinoid receptors that we have in our brain, and the various parts of our body.
Whereas CBD has a low affinity for those, it still binds with them, but less affinity, and it acts through lots of different other receptors.
So like the serotonin receptors, for example.
So they work through different mechanisms of action if you like but they've both got some similar actions.
So there's analgesic effects, pain relieving effects, anti inflammatory effects, antioxidant effects, and a whole raft of beneficial effects that both THC and CBD have. But CBD has some special sort of actions in that it's anxiolytic whereas too much THC can actually cause anxiety. It's anti psychotic, it's also anti seizure.
So you find a lot of the clinical studies in CBD have been conducted into severe forms of epilepsy, for example.
Kel: Yeah.
Dr Kylie O'Brien: So they're kind of the main sort of differences, I suppose, but, you know, they complement each other and usually you'll find in, in oils, for example, that is if you've got a high THC oil, you're going to have some CBD in there and supposedly the CBD can help mitigate some of the perhaps more undesirable effects of side effects of THC as well as improve its good effects.
So they're often combined together. So in our Project Formulary, for example, we've got both flower products and oil products.
With the oils, we've got a high CBD product. We've got a balanced, which means the CBD and THC ratios around about the same. And then we've got a high THC oil. With the flower, we've got a number of different what they call cultivated varieties or cultivars of flowers.
And again, because they've got different phytochemical profiles, they could have slightly different effects, therapeutic effects on the body.
And the reason we've got different types of things is that different cultivars and different types of products will be individualised to the patient. So it's not like you all get the same thing: plant medicines don't work like that.
And I guess the flower, for example, has a fast onset.
You inhale something, its onset of action is really fast, you know, five to ten minutes, but it lasts, say, two to four hours. The oils have a slower onset of action, maybe one to three hours, but they have longer lasting effects, six to eight hours.
So, in this study, it's an observational study. It's not a randomised controlled trial. So an observational study.
We are collecting real world data and the cannabis products are going to be individualised to the patient and as I said, prescribed through a doctor at the Natura Healthcare Clinic.
So, depending on what the other health issues that the patient might present with, the doctor will choose the particular product or maybe a combination of products for that patient and the patient of course will remain under the care of the doctor during the study.
Kel: Thank you so much for taking the time to explain those distinctions and provide some clarity.
I think that's, that's just so helpful to the audience to just understand the basic building blocks of medicinal cannabis so they can go on their own educational journey from there. So thank you so much for that. Just moving on to impact, given how individualised medicinal cannabis is, how do you measure success of a study like this?
Dr Kylie O'Brien: Yeah, that's a great question.
Look you go into a study, you set up your hypothesis and you measure what we call outcome variables. So in this case, our main or primary outcome variable is the severity of the menstrual pain associated with primary dysmenorrhea and it's going to be measured on a zero to ten numerical rating scale.
So that's the first thing that they record in a menstrual diary during the first three days of the menses.
But then they are sent other questionnaires which are filled in online.
So you know, there's a premenstrual symptom screening test, for example, that asks about anxiety and tension and sleep and work efficiency leading up to the period.
We've got a quality of life questionnaire in there.
We've got a questionnaire about menstrual flow, pharmaceutical use- whether they have to use rescue medication like a non steroidals or, you know, or other kind of painkillers. We're also tracking safety data. So we ask them to log any side effects each month as part of the questionnaires.
But of course, if they had any sort of side effects that were more serious then they need to obviously contact the doctor immediately, etc.
And we're also doing some blood tests for safety.
So at baseline, three months and six months, they have to have some blood tests where we're tracking just to make sure that there are no changes to, for example, liver or kidney function.
And we're also got a cannabis use disorder questionnaire at the end of the study too, because we want to, you know, ensure that those who were taking THC medicines haven't developed any sort of cannabis use disorder, for example.
So they're the main things that we're kind of tracking, I guess, in the study.
Kel: I love the fact that you're taking an entire view, like the quality of life aspect of it and it's not just one thing and just the understanding that, you know, painful periods, obviously there's going to be anxiety, there's going to be depression, there's going to be these horrible side effects because, you know, it's affecting your quality of life ultimately.
Dr Kylie O'Brien: Of course it is.
Kel: Yeah, I love that holistic approach.
Dr Kylie O'Brien: Yeah. I mean those sorts of things are very important because those sorts of things make life a bit of misery, don't they, if you're always anxious or you're, you know, you're not getting proper sleep. You know, the, the flow on effect is an enormous cost to women, but it's also an enormous cost to society as well in terms of, you know, absenteeism from study or work or, you know, if you're able to show up then, you know, not being effective at work, things like that.
They're all important things that impact not only on the individual, of course, but, you know, there's a social cost as well and an economic cost, I guess, too.
Yeah, yeah, most definitely. I think in terms of findings, I know it's still quite early days. Is it April that the study began? Yeah. Yeah, yeah. Have you found anything that stood out yet?
No, not really.
Yeah. Way too early. No, we've only just started recruiting. We've just started to have our first few participants sort of come through and be prescribed. So we're very much at the starting gates, but I'm hoping next year that we might be able to jump on this podcast again, and I can actually you know, report on what we found.
Kel: I would love that. Yeah. Thank you. That'd be, that'd be beautiful. I think. This kind of study is obviously groundbreaking in many ways, as you explained at the start, and we're very much at the beginning of the journey, research wise, in terms of medicinal cannabis here and just globally in general, especially when it comes to women's health and addressing these issues.
What are some of the biggest challenges in conducting a study like this? Especially considering that, even though, you Cannabis is legal, there's still some stigma around it in society today.
Dr Kylie O'Brien: Yeah, and I think that's right.
It is about breaking down the stigma because, you know, it's only in recent times, 2016, that it became available for medical use in this country.
It's still considered an unapproved medicine by the Therapeutic Goods Administration, which means it can only be prescribed by a doctor in some states, as a nurse practitioner, but, you know, so but there's a legacy of all the, the I guess in some ways, a lot of propaganda you know, when it was first prohibited in the U. S. and other countries sort of followed suit back in the 1930s.
There's a lot of stigma around it, a lot of misunderstanding, a lot of doctors don't understand a lot about it and so they would rather sort of, you know, in some cases ignore it or dismiss it rather than sort of look into it.
So I think, you know, in a lot of cases, it's the patients coming forward and saying, well, I'm interested in this.
And look, recruitment's always a challenge in conducting research.
I don't think it matters what study you'd sort of doing. It's always, you know difficult to recruit because it's trying to get the message out there to a target group that might be interested in being part of a, you know, a clinical study.
So I guess they're just some of the challenges, but I think you probably hit the nail on the head actually, is it, you know, there's this stigma around it. But that's gradually being broken down as more and more doctors are becoming educated, pharmacists as well, become educated about it. And that's not to say it's a magic bullet.
It's you know, there are safety aspects that need to be considered.
It's not for everyone.
But it can be useful in some conditions. It's just that the evidence base is growing, if you like. There's a lot of, preclinical research, research in cells and animals and things like that.
There's less research in humans in general, across the board with medicinal cannabis. And so, you know, there's less to, I guess reassure doctors that it could be useful. So that's part of it as well. We need to grow the evidence base.
To find out either way, is it useful for this condition or not?
Is it safe in this condition or not?
And we have to be also, as researchers, be willing to, to find out it doesn't work for something. You know, that's, that's part of being a researcher.
Kel: Yeah, that science, isn't it? It's just as important to be able to disprove something as it is to say, yes, this is, this works.
Dr Kylie O'Brien: Yeah.
Kel: Absolutely. Yeah. And, you know, I think that, yeah, there is that stigma and I think we're in this funny kind of transformational period at the moment where there's so much more focus on just patient led care, patient advocacy and people just really taking charge of their health.
And I think that's helping to offset some of maybe the clinical lack of understanding or misinformation. Yeah, yeah. So yeah, interesting times.
What impact do you think this study will have on on future research around period pain management and women's health more generally? What are you expecting to see maybe happen?
Dr Kylie O'Brien: This is a modest, I call it a pilot study, it's a small study and it's observational.
So the advantage of an observational study is that we're really looking at people under real world conditions and using it over more extended time periods, in this case six months.
So we're really working out. at a basic level, look, does medicinal cannabis appear to, to work or not?
And which, you know, of those subtypes of cannabis products might be effective or not?
Now, if we do find that it looks like that there is evidence of effectiveness that would be a signal to us that, you know, that, you know, Keep going with the research. It might be worth looking at it in more depth for period pain.
You'd obviously need much larger scale studies to more definitively investigate whether medicinal cannabis is effective or not though.
So, you know, I'm under no illusions. Our first study here being conducted by the NICM Health Research Institute is very much a pilot study, very early days, but if we do find that this is showing promise, then that would, you know, that would say, all right maybe we go into a much larger study now.
And that could include a randomised controlled trial type of study design in the future as well.
Kel: Just moving on to listeners considering medicinal cannabis who are maybe or maybe have tried it and not had success and maybe want to give it a go again. What advice would you give to someone considering this to treat menstrual pain related symptoms?
And yeah, what steps should people take to approach it responsibly? And I want to also add in there, so it's sustainable for them as well.
Dr Kylie O'Brien: That's right.
Well, look, as I said earlier, medicinal cannabis is an unapproved good in Australia.
Cannabidiol products, mostly, not all, but most of them are Schedule 4 (Prescription only) medicines.
Most of the Products containing THC are Schedule 8 (Controlled drugs), so they have to be prescribed by a doctor.
So I would say that anyone who's contemplating medicinal cannabis treatment for period pain should consult a doctor who's trained in medicinal cannabis to find out whether it's the best option for them or not.
If it's period pain and they don't know what's causing it, obviously they would need to investigate that first because it could be a secondary condition there that's causing it, that needs treatment, right?
But if it was primary dysmenorrhea and everything else had been ruled out then, you know, if they wanted to look at medicinal cannabis, then I'd say, well, look, talk to your regular GP if your regular GP is, is open minded about it or open to it.
You know, consult someone who's trained in medicinal cannabis specifically. There are a lot of doctors now who are Authorized Prescribers of medicinal cannabis or prescribe through the Special Access Scheme B, they're both TGA schemes to prescribe medicinal cannabis. So and that doctor can then decide whether it's, You know, the right thing for them or not, because as I said, it's not for everyone.
Some components of medicinal cannabis, like CBD and, and THC, they can interact with some pharmaceutical drugs, for example. And medicinal cannabis needs to be dosed properly. Otherwise, it could cause, you know, some undesirable side effects. So, a doctor can help or a nurse practitioner can help guide the patient in how to do that:achieve the right dosage that's appropriate for them. I don't recommend having a crack at it yourself or using anything from the black market or gray market. You don't know the quality of those products that are on the more illicit market, if you like.
The TGA does some great stuff, and part of what it does well is quality control of medicines and complementary medicines in Australia. So all those products that are on the legal market, have to hold evidence of quality to be able to be on the market.
So I would always advise people go the legal route.
Get advice from a doctor trained in it and individualised for you.
And you know, that might take a little bit of tweaking to work out what the dose is, the right dose for you is, the right products for you are.
So yeah, I think just, just be sensible and safe about it.
And as I said, it, it isn't for everyone. And and I guess the reason it's still an unapproved good is, you know, because the evidence base is still building around it..
Kel: Thank you so much Kylie. That's so helpful and insightful and just moving on now to final thoughts as we, as we wrap up Could you share a key takeaway that you hope the public, the general public will understand about medicinal cannabis and its potential benefits for period pain, but also just more broadly, what's like one thing you'd like people to know?
Dr Kylie O'Brien: Well, I think I think it's important to realise medicinal cannabis, as I said earlier, is not one thing. There are many different types of cannabis products with different phytochemical profiles. And I just reiterate, if you're considering it, go and see a doctor trained in it who can assess whether it's right for you or not.
And I think it's important to realise at this point, there is a lack of scientific evidence for its use in primary dysmenorrhea, which is exactly why we're doing this study. And as I said I hope to be able to report on the results back here sometime next year.
Kel: I'll very much look forward to that, Kylie.
And I'll make sure that the link to the study is in the show notes, so anybody that's interested in finding out more can, can take a look at that. as well. And all the best with the study and yeah, I look forward to catching up again soon.
Dr Kylie O'Brien: Thanks very much, Kel.
Kel: Thanks so much, Kylie.
And that dear listeners brings to close my conversation with Dr. Kylie O'Brien.
For more information on the Lumir Mission Plant Based Medicine for Primary Dysmenorrhea Study, please visit the show notes or search online.
Until next time, I'm Kel Myers and this is Phoenix Sound.
View all episodes
By Rising above the status quo, one conversation at a timeFor more info on The Lumir Mission Plant-based Medicine for Primary Dysmenorrhoea (Period Pain) Study head here
TRANSCRIPT
Kel: I'm Kel Myers and you're listening to Phoenix Sound.
In today's episode, I'm thrilled to welcome Dr. Kylie O'Brien, Chief Scientific Officer at Cannim Group.
Under her leadership, Cannim is sponsoring the Lumir Mission plant based medicine for primary dysmenorrhea study, conducted by the NICM Health Research Institute.
This study investigates the potential of plant based medicine to alleviate period pain. A condition that many women and girls endure in in silence because it's often dismissed as normal.
Having experienced debilitating periods for decades myself before being diagnosed with endometriosis four years ago, I understand the effect period pain can have on a person's life and how hard it is to find relief.
In the quest to find effective treatment, Dr. Kylie is at the forefront of promoting education and advocacy in her field. And today we'll dive into the scientific endeavors and goals of this crucial research, uncovering what makes this study such a significant leap forward in women's health. Stay with hi Kylie.
So can you give us an overview of the medicinal cannabis for primary dysmenorrhea study and what prompted the research team to explore this specific area?
Dr Kylie O'Brien: Well it’s a longitudinal, prospective, observational study in 65 women who are aged 20 years or over who are suffering from Primary Dysmenorrhea.
And it'll investigate the effectiveness of medicinal cannabis over six months.
So, Primary Dysmenorrhea is period pain which is not associated with any kind of pathology in the pelvis.
So, in this study, participants will have a consultation with a medical doctor and be prescribed the medicinal cannabis products from a project formulary and they'll complete various questionnaires at baseline and then monthly online. So, study's been conducted by the NICM Health Research Institute at Western Sydney University.
So, the, the NICM Health Research Institute, one of the top research institutes for research into plant based medicines, including medicinal cannabis.
So I guess the key aim of the study is to investigate whether medicinal cannabis products as a whole, as well as specific subcategories, which we call chemotypes of products are effective in alleviating pelvic pain associated with Primary dysmenorrhea, as well as some of the other symptoms that you get associated with it.
And I'll just explain those terms.
Chemotype One is a high THC cannabis product.
Chemotype Two is a balanced product where you get similar ratios of the two major phyto cannabinoids, Tetra hydro cannabinol, or THC and cannabidiol or CBD.
And then the Chemotype Three is the high CBD with low THC types of products.
So when you ask about what prompted us to explore this specific area of health, well, I guess it's been a lot of research conducted into different forms of chronic pain. And there's some evidence from systematic reviews that indicates that medicinal cannabis might be able to alleviate at least some forms of chronic pain.
And when I looked into it I found that there haven't been a lot of studies specifically in primary dysmenorrhea.
So there was a large, what they call systematic review of medicinal cannabis use for gynaecological pain and that was 16 studies.
And a subset of, set of that was seven studies, which were seven cross sectional surveys, which investigated whether cannabis to treat gynaecological pain was useful or not.
And in that study, they found that the prevalence of cannabis use was anywhere between 13 and 27 percent across four of those studies.
The rate of pain relief was anywhere between 61 and 95 percent across Six studies.
Kel: Wow. They're huge numbers, aren't they? 61. Can you just say that again? 61 to 90.
Dr Kylie O'Brien: 95%. So the rate of pain relief across the six studies that looked at this found that the rate of pain relief was anywhere between 61 and 95%. And some of the studies, interestingly, also found that medicinal cannabis use was associated with decreased analgesic use, including opioids.
But the thing was, none of those studies were specifically in primary dysmenorrhea.
They were in gynaecological pain due to a number of different things. But none in primary dysmenorrhea.
Then I found another study that was done in Australia.
It was qualitative research. It was like a focus group in 26 women with primary dysmenorrhea this time, and it found that the current treatment strategies like non-steroidal anti-inflammatory drugs and heat and other non-pharmaceutical management didn't provide adequate pain control and there was a dissatisfaction with the current management strategies like over the counter analgesics was a key driver for these particular women wanting to use medicinal cannabis.
So up until then when I first did the literature research, that was largely what I found.
But then recently I found a study had been published in Cannabidiol Isolate, which suggests that it may reduce menstruation related symptoms like anxiety and irritability and stress.
So and of course there's studies in other populations that indicate that medicinal cannabis might be effective for things like anxiety and poor sleep. And so those are often also there -they call them comorbidities as well as the pain in primary dysmenorrhea.
So we've got a few studies that are sort of pointing in the right direction saying well possibly this might work for primary dysmenorrhea but there really is a lack of, of clinical research to be able to guide practitioners into whether you know medicinal cannabis might be a suitable option for women who aren't responding to say orthodox strategies.
And I suppose the other bit of interesting stuff is that when you look in the animal research they have found and other forms of research, cell research, they call that preclinical research, we do know that components of medicinal cannabis have got anti inflammatory actions, as well as analgesic actions, we do know from studies in animal models that THC and a, what they call a synthetic isomer of CBD, as well as agonists, of the cannabinoid receptors in the body can reduce excessive myometrial contractility in animal models.
And that's part of what causes the pain in primary dysmenorrhea is that you get excess contractility of the muscle layer in the uterus.
So, I guess when you look at it, the endocannabinoid system, a lot of people don't understand that we've got this regulatory neuro- and immuno- regulatory system in the body that regulates most bodily systems, if not all of them.
And it's very relevant to primary dysmenorrhea because we have the endocannabinoid system components in the reproductive organs.
So the endocannabinoid system regulates analgesia and pain, stress and emotions, sleep, nausea and vomiting. It regulates so many different things in the body. I've just read out some of the ones that are kind of relevant to primary dysmenorrhea.
And the other thing is that components of medicinal cannabis, can interact with that endocannabinoid system. So when you put all that together, you think, all right, well, there is some rationale for bothering to go into some clinical research, at least some preliminary research, which is what we're doing.
It's a small study in women with primary dysmenorrhea to find out, well, could it be effective or not?
Kel: Yeah, I'd love to come back to the CBD and the THC and the distinction between the two in a minute. But I'll just park that for a second while we just go through the research methodology.
I'm just wondering what the criteria was for selecting participants and how do you ensure that the treatment is suitable given how complex medicinal cannabis is.
Dr Kylie O'Brien: Yeah, well look like any other substance study there are definite inclusion criteria and exclusion criteria for coming into a study.
So some of the inclusion criteria, I won't read them all out, but obviously they've got to have primary dysmenorrhea not secondary dysmenorrhea, so secondary dsymenorrhea is period pain, but it's due to a pathology like endometriosis, for example.
So we're working with primary dysmenorrhea.
The participants have to be 20 years or over and not used cannabis within the last three months.
They've got to be willing to undertake some safety blood tests and be able and willing to complete the study questionnaires sent to them and be obviously willing to give informed consent to be part of the study. And they've got to be willing to use contraception for the duration of the study.
And they're the sort of standard things I guess you'd expect in a clinical study.
And then there's a range of exclusion criteria.
So for example you know, a, a current medical condition, which in the opinion of the study coordinator or the medicinal cannabis doctor who's going to be involved in the study is a contraindication for medicinal cannabis; if they're pregnant or planning to become pregnant during the study duration then they can't come into the study; if they're not willing to use contraception for the duration of the study.
So there's a number of different inclusion and exclusion criteria that if people are interested in looking at, our participating clinic the Natura Healthcare Clinic website has the details for that.
But look, at the end of the day, even if someone was screened and look, they met the inclusion criteria and didn't have any of those exclusion criteria, and they came into the study the first, I guess, step is that they have to have a consultation with a doctor through Natura Healthcare Clinic.
And that doctor will really ultimately decide -are they suitable for treatment with medicinal cannabis or not? And if the doctor says, "I don't think medicinal cannabis is actually suitable for you", for whatever reason, then it's not going to be prescribed and that potential participant wouldn't be able to continue in the study.
So at the end of the day I guess the medical doctor has the last word on whether someone comes into the study.
Kel: Now, just circling back to medicinal cannabis and its role, I think, you know, there's a lot of misinformation and pseudoscience that orbits around medicinal cannabis, as you, you will well know.
Distorting what it is and how it works in the body. Yes. And particularly, I think, when it comes to the distinction between CBD and THC. Yes. Now, for those who are new to the space, like many of us, people are, most of the general public are seeking clarity. I'd love it if you could explain the differences just on a basic level of say high THC versus high CBD formulations.
And also as well, just an additional point, what types of medicinal cannabis products are being used in the study? I'd love to know that too - thank you.
Dr Kylie O'Brien: Two great questions. And look, medicinal cannabis, cannabis has, you know, it has almost 2000 constituents in it.
There's probably now well over 200 what they call phyto cannabinoids.
And they've got many different terpenes.
The terpenes are essential oil like substances that give the plant its characteristic smell, and you've got many other plant nutrients.
So it's not just one thing, but mostly people hear about the two major phyto cannabinoids: tetrahydrocannabinol or THC and cannabidiol or CBD.
But there are other minor phyto cannabinoids as well, and they've got therapeutic actions.
So it's believed that the combination of all these plant nutrients is what helps determine the therapeutic action of different medicinal cannabis products.
So it's not just one thing in other words.
So it's not just CBD and THC. They call that the entourage effect where it's the other plant nutrients are adding to the overall therapeutic effect.
So medicinal cannabis is not one thing. It's not just one product.
And depending on what's in that medicinal cannabis product, that may impact on the therapeutic effect.
So THC and CBD are the two main phytocannabinoids. The main difference, I suppose, is that THC is the only phytocannabinoid that is associated with that potentially euphoric effect that you associate with, you know, for example, the smoking of cannabis recreationally or for adult use.
CBD does not have that potentially euphoric effect.
And I say potentially because it's dose dependent.
So, you know, with THC, if you have a small amount of THC, that's not going to cause that euphoria. If you have a large amount, yes, it could, as well as a whole lot of other perhaps less desirable side effects as well.
I think there's a big misconception that cannabis is one thing and you know, when it's actually not.
So CBD is not addictive. It doesn't havethat potential euphoria like THC can do.
But it's not to say it's not psychoactive because it's anxiolytic which means it can reduce anxiety for example.
So it does have an effect you know on your psyche if you like.
So the two of them, they work in different ways, so THC is what they call a partial agonist, which means it binds with the cannabinoid receptors that we have in our brain, and the various parts of our body.
Whereas CBD has a low affinity for those, it still binds with them, but less affinity, and it acts through lots of different other receptors.
So like the serotonin receptors, for example.
So they work through different mechanisms of action if you like but they've both got some similar actions.
So there's analgesic effects, pain relieving effects, anti inflammatory effects, antioxidant effects, and a whole raft of beneficial effects that both THC and CBD have. But CBD has some special sort of actions in that it's anxiolytic whereas too much THC can actually cause anxiety. It's anti psychotic, it's also anti seizure.
So you find a lot of the clinical studies in CBD have been conducted into severe forms of epilepsy, for example.
Kel: Yeah.
Dr Kylie O'Brien: So they're kind of the main sort of differences, I suppose, but, you know, they complement each other and usually you'll find in, in oils, for example, that is if you've got a high THC oil, you're going to have some CBD in there and supposedly the CBD can help mitigate some of the perhaps more undesirable effects of side effects of THC as well as improve its good effects.
So they're often combined together. So in our Project Formulary, for example, we've got both flower products and oil products.
With the oils, we've got a high CBD product. We've got a balanced, which means the CBD and THC ratios around about the same. And then we've got a high THC oil. With the flower, we've got a number of different what they call cultivated varieties or cultivars of flowers.
And again, because they've got different phytochemical profiles, they could have slightly different effects, therapeutic effects on the body.
And the reason we've got different types of things is that different cultivars and different types of products will be individualised to the patient. So it's not like you all get the same thing: plant medicines don't work like that.
And I guess the flower, for example, has a fast onset.
You inhale something, its onset of action is really fast, you know, five to ten minutes, but it lasts, say, two to four hours. The oils have a slower onset of action, maybe one to three hours, but they have longer lasting effects, six to eight hours.
So, in this study, it's an observational study. It's not a randomised controlled trial. So an observational study.
We are collecting real world data and the cannabis products are going to be individualised to the patient and as I said, prescribed through a doctor at the Natura Healthcare Clinic.
So, depending on what the other health issues that the patient might present with, the doctor will choose the particular product or maybe a combination of products for that patient and the patient of course will remain under the care of the doctor during the study.
Kel: Thank you so much for taking the time to explain those distinctions and provide some clarity.
I think that's, that's just so helpful to the audience to just understand the basic building blocks of medicinal cannabis so they can go on their own educational journey from there. So thank you so much for that. Just moving on to impact, given how individualised medicinal cannabis is, how do you measure success of a study like this?
Dr Kylie O'Brien: Yeah, that's a great question.
Look you go into a study, you set up your hypothesis and you measure what we call outcome variables. So in this case, our main or primary outcome variable is the severity of the menstrual pain associated with primary dysmenorrhea and it's going to be measured on a zero to ten numerical rating scale.
So that's the first thing that they record in a menstrual diary during the first three days of the menses.
But then they are sent other questionnaires which are filled in online.
So you know, there's a premenstrual symptom screening test, for example, that asks about anxiety and tension and sleep and work efficiency leading up to the period.
We've got a quality of life questionnaire in there.
We've got a questionnaire about menstrual flow, pharmaceutical use- whether they have to use rescue medication like a non steroidals or, you know, or other kind of painkillers. We're also tracking safety data. So we ask them to log any side effects each month as part of the questionnaires.
But of course, if they had any sort of side effects that were more serious then they need to obviously contact the doctor immediately, etc.
And we're also doing some blood tests for safety.
So at baseline, three months and six months, they have to have some blood tests where we're tracking just to make sure that there are no changes to, for example, liver or kidney function.
And we're also got a cannabis use disorder questionnaire at the end of the study too, because we want to, you know, ensure that those who were taking THC medicines haven't developed any sort of cannabis use disorder, for example.
So they're the main things that we're kind of tracking, I guess, in the study.
Kel: I love the fact that you're taking an entire view, like the quality of life aspect of it and it's not just one thing and just the understanding that, you know, painful periods, obviously there's going to be anxiety, there's going to be depression, there's going to be these horrible side effects because, you know, it's affecting your quality of life ultimately.
Dr Kylie O'Brien: Of course it is.
Kel: Yeah, I love that holistic approach.
Dr Kylie O'Brien: Yeah. I mean those sorts of things are very important because those sorts of things make life a bit of misery, don't they, if you're always anxious or you're, you know, you're not getting proper sleep. You know, the, the flow on effect is an enormous cost to women, but it's also an enormous cost to society as well in terms of, you know, absenteeism from study or work or, you know, if you're able to show up then, you know, not being effective at work, things like that.
They're all important things that impact not only on the individual, of course, but, you know, there's a social cost as well and an economic cost, I guess, too.
Yeah, yeah, most definitely. I think in terms of findings, I know it's still quite early days. Is it April that the study began? Yeah. Yeah, yeah. Have you found anything that stood out yet?
No, not really.
Yeah. Way too early. No, we've only just started recruiting. We've just started to have our first few participants sort of come through and be prescribed. So we're very much at the starting gates, but I'm hoping next year that we might be able to jump on this podcast again, and I can actually you know, report on what we found.
Kel: I would love that. Yeah. Thank you. That'd be, that'd be beautiful. I think. This kind of study is obviously groundbreaking in many ways, as you explained at the start, and we're very much at the beginning of the journey, research wise, in terms of medicinal cannabis here and just globally in general, especially when it comes to women's health and addressing these issues.
What are some of the biggest challenges in conducting a study like this? Especially considering that, even though, you Cannabis is legal, there's still some stigma around it in society today.
Dr Kylie O'Brien: Yeah, and I think that's right.
It is about breaking down the stigma because, you know, it's only in recent times, 2016, that it became available for medical use in this country.
It's still considered an unapproved medicine by the Therapeutic Goods Administration, which means it can only be prescribed by a doctor in some states, as a nurse practitioner, but, you know, so but there's a legacy of all the, the I guess in some ways, a lot of propaganda you know, when it was first prohibited in the U. S. and other countries sort of followed suit back in the 1930s.
There's a lot of stigma around it, a lot of misunderstanding, a lot of doctors don't understand a lot about it and so they would rather sort of, you know, in some cases ignore it or dismiss it rather than sort of look into it.
So I think, you know, in a lot of cases, it's the patients coming forward and saying, well, I'm interested in this.
And look, recruitment's always a challenge in conducting research.
I don't think it matters what study you'd sort of doing. It's always, you know difficult to recruit because it's trying to get the message out there to a target group that might be interested in being part of a, you know, a clinical study.
So I guess they're just some of the challenges, but I think you probably hit the nail on the head actually, is it, you know, there's this stigma around it. But that's gradually being broken down as more and more doctors are becoming educated, pharmacists as well, become educated about it. And that's not to say it's a magic bullet.
It's you know, there are safety aspects that need to be considered.
It's not for everyone.
But it can be useful in some conditions. It's just that the evidence base is growing, if you like. There's a lot of, preclinical research, research in cells and animals and things like that.
There's less research in humans in general, across the board with medicinal cannabis. And so, you know, there's less to, I guess reassure doctors that it could be useful. So that's part of it as well. We need to grow the evidence base.
To find out either way, is it useful for this condition or not?
Is it safe in this condition or not?
And we have to be also, as researchers, be willing to, to find out it doesn't work for something. You know, that's, that's part of being a researcher.
Kel: Yeah, that science, isn't it? It's just as important to be able to disprove something as it is to say, yes, this is, this works.
Dr Kylie O'Brien: Yeah.
Kel: Absolutely. Yeah. And, you know, I think that, yeah, there is that stigma and I think we're in this funny kind of transformational period at the moment where there's so much more focus on just patient led care, patient advocacy and people just really taking charge of their health.
And I think that's helping to offset some of maybe the clinical lack of understanding or misinformation. Yeah, yeah. So yeah, interesting times.
What impact do you think this study will have on on future research around period pain management and women's health more generally? What are you expecting to see maybe happen?
Dr Kylie O'Brien: This is a modest, I call it a pilot study, it's a small study and it's observational.
So the advantage of an observational study is that we're really looking at people under real world conditions and using it over more extended time periods, in this case six months.
So we're really working out. at a basic level, look, does medicinal cannabis appear to, to work or not?
And which, you know, of those subtypes of cannabis products might be effective or not?
Now, if we do find that it looks like that there is evidence of effectiveness that would be a signal to us that, you know, that, you know, Keep going with the research. It might be worth looking at it in more depth for period pain.
You'd obviously need much larger scale studies to more definitively investigate whether medicinal cannabis is effective or not though.
So, you know, I'm under no illusions. Our first study here being conducted by the NICM Health Research Institute is very much a pilot study, very early days, but if we do find that this is showing promise, then that would, you know, that would say, all right maybe we go into a much larger study now.
And that could include a randomised controlled trial type of study design in the future as well.
Kel: Just moving on to listeners considering medicinal cannabis who are maybe or maybe have tried it and not had success and maybe want to give it a go again. What advice would you give to someone considering this to treat menstrual pain related symptoms?
And yeah, what steps should people take to approach it responsibly? And I want to also add in there, so it's sustainable for them as well.
Dr Kylie O'Brien: That's right.
Well, look, as I said earlier, medicinal cannabis is an unapproved good in Australia.
Cannabidiol products, mostly, not all, but most of them are Schedule 4 (Prescription only) medicines.
Most of the Products containing THC are Schedule 8 (Controlled drugs), so they have to be prescribed by a doctor.
So I would say that anyone who's contemplating medicinal cannabis treatment for period pain should consult a doctor who's trained in medicinal cannabis to find out whether it's the best option for them or not.
If it's period pain and they don't know what's causing it, obviously they would need to investigate that first because it could be a secondary condition there that's causing it, that needs treatment, right?
But if it was primary dysmenorrhea and everything else had been ruled out then, you know, if they wanted to look at medicinal cannabis, then I'd say, well, look, talk to your regular GP if your regular GP is, is open minded about it or open to it.
You know, consult someone who's trained in medicinal cannabis specifically. There are a lot of doctors now who are Authorized Prescribers of medicinal cannabis or prescribe through the Special Access Scheme B, they're both TGA schemes to prescribe medicinal cannabis. So and that doctor can then decide whether it's, You know, the right thing for them or not, because as I said, it's not for everyone.
Some components of medicinal cannabis, like CBD and, and THC, they can interact with some pharmaceutical drugs, for example. And medicinal cannabis needs to be dosed properly. Otherwise, it could cause, you know, some undesirable side effects. So, a doctor can help or a nurse practitioner can help guide the patient in how to do that:achieve the right dosage that's appropriate for them. I don't recommend having a crack at it yourself or using anything from the black market or gray market. You don't know the quality of those products that are on the more illicit market, if you like.
The TGA does some great stuff, and part of what it does well is quality control of medicines and complementary medicines in Australia. So all those products that are on the legal market, have to hold evidence of quality to be able to be on the market.
So I would always advise people go the legal route.
Get advice from a doctor trained in it and individualised for you.
And you know, that might take a little bit of tweaking to work out what the dose is, the right dose for you is, the right products for you are.
So yeah, I think just, just be sensible and safe about it.
And as I said, it, it isn't for everyone. And and I guess the reason it's still an unapproved good is, you know, because the evidence base is still building around it..
Kel: Thank you so much Kylie. That's so helpful and insightful and just moving on now to final thoughts as we, as we wrap up Could you share a key takeaway that you hope the public, the general public will understand about medicinal cannabis and its potential benefits for period pain, but also just more broadly, what's like one thing you'd like people to know?
Dr Kylie O'Brien: Well, I think I think it's important to realise medicinal cannabis, as I said earlier, is not one thing. There are many different types of cannabis products with different phytochemical profiles. And I just reiterate, if you're considering it, go and see a doctor trained in it who can assess whether it's right for you or not.
And I think it's important to realise at this point, there is a lack of scientific evidence for its use in primary dysmenorrhea, which is exactly why we're doing this study. And as I said I hope to be able to report on the results back here sometime next year.
Kel: I'll very much look forward to that, Kylie.
And I'll make sure that the link to the study is in the show notes, so anybody that's interested in finding out more can, can take a look at that. as well. And all the best with the study and yeah, I look forward to catching up again soon.
Dr Kylie O'Brien: Thanks very much, Kel.
Kel: Thanks so much, Kylie.
And that dear listeners brings to close my conversation with Dr. Kylie O'Brien.
For more information on the Lumir Mission Plant Based Medicine for Primary Dysmenorrhea Study, please visit the show notes or search online.
Until next time, I'm Kel Myers and this is Phoenix Sound.