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Is medical marijuana the next wonder drug?

25 September 2017

People involved in medical cannabis can find themselves in a twilight zone where the law may prevent its use after other treatments fail. Professor Iain McGregor explains the vision, stories and studies behind the Lambert Initiative.

This episode from the University of Sydney podcast Open for Discussionabout the Lambert Initiative for Cannabinoid Therapeutics, puts the spotlight on the complex cannabis plant, compares community-use regulations in different countries and highlights the pioneering research happening in Australia that could lead to the development of new, more effective and potentially life-saving medicines.

Host: Dr Chris Neff
Guest: Professor Iain McGregor
Producers: Vivienne Reiner, Verity Leatherdale
Editor: Caitlin Gibson

 

Professor Iain McGregor
Professor McGregor is the Academic Director of the Lambert Initiative and an NHMRC Principal Research Fellow.

Evidence gap

“There’s this kind of evidence gap, which means that a lot of the key clinical studies are yet to be done," said Professor Iain McGregor.

“Cancer’s a great example. We hear stories every week of cancer patients who have been taking cannabis products and show a reduction in tumour size, who feel healthier, who are getting relief from pain, from nausea and so on.

“But in the case of shrinking cancer cells, there’s not one good human clinical trial that’s been done. It’s almost unbelievable when you hear all the anecdotes, all the stories, some of them quite remarkable.

“We had a young woman come to the Lambert Initiative a few weeks ago who recounted a story where she’d been given six weeks to live with an inoperable upper gastro-intestinal tumor and had been given only a few weeks to live.

“And she started bombarding that tumor with high THC oil and experienced full remission.

“Now we don’t have a large clinical trial featuring 100, 200, 400 patients with the same sort of cancer that’s placebo controlled.

“We hear this anecdote, we hear these single case studies that are quite remarkable yet the overwhelming clinical gold standard evidence that doctors typically need, is not present.

“So, quite rightly in some cases, doctors are extremely cautious and risk averse about encouraging their patients to use cannabis products when that evidence base is not in place.

“Cannabis is an outlier, it doesn’t really adhere to the standard pharmaceutical medical model.”

Plant composition

“Within the cannabis plant we have something like 400 different bioactive molecules.

“Most people know THC, which is the one that gets you intoxicated but there’s many, many other cannabinoids. There was 106 last count as well as flavonoids and terpenes and other categories of chemicals - and just about all of them have some sort of therapeutic potential.

“What the Lambert Initiative is doing is to try and get a short list of the most promising candidates for a variety of different diseases.”

Regulation

“The scheme that has been rolled out in Australia, we really only have a handful of people [in the community] that are currently being given access.

“And there’s a problem there in that we know that in the community there may be something between 50 and 200,000 patients who are using medicinal cannabis in Australia illegally.

What the Lambert Initiative is doing is to try and get a short list of the most promising candidates for a variety of different diseases.
Professor Iain McGregor

“…the overwhelming majority of Australians want compassionate access to medicinal cannabis for people who have intractable pain, who have epilepsy, who have unbearable conditions.

“It may take months, it may take years, it may take a revolution but it’s inevitable that the community will get what they want.”

Funding

“…to do a good clinical trial can often be a 5 to 10 million dollar project so … in some ways we can only do three big clinical trials with the money that we have; so our model is more to seed projects.

“It was an inspired gift [$33.7 million] from the Lamberts to the University of Sydney.

“It’s enough money to really make a difference and to attract other people and we’ll snowball that money into something that will, hopefully, be unstoppable.”

Donate to the Lambert Initiative via piecemakerdesign.com/lambert/donate.html

Find out more about the University of Sydney’s philanthropic campaign INSPIRED

Listen online to this Open for Discussion podcast via SoundCloud

Transcript

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Chris Neff: People taking medical cannabis can find themselves in a twilight zone where the law may prevent the use of medical marijuana despite the evidence that it could save their lives. So how is it that we have a centre, the Lambert Initiative, funded by a record 34 million-dollar donation to the University of Sydney that’s demonstrating overwhelmingly positive results and yet some legal roadblocks.

With me today on Open for Discussion is Professor Iain McGregor, academic director at The University of Sydney’s Lambert Initiative who is here to tell us the story behind the Lambert Initiative and explain its hopes for drug discovery.

So Iain, thanks so much for joining us.

Professor Iain McGregor: It’s great to be here.

Chris Neff: How did you first get involved in medical cannabis?             

Professor Iain McGregor: I think I was just very curious about drugs in general and how they could change the human mind and how they interacted with the brain and the body. 

That got me into studying psychology and I was lucky enough to get a scholarship way back then to go down to Oxford which I ... the psychology department down there was very brain based so I ended up learning a lot about neurochemistry and pharmacology and what we call phychopharmacology, which is the interaction between drugs and the brain and behaviour.

And so, I’m interested in a wide range of drugs, both illegal drugs and prescription drugs and how they affect the brain and how they affect the human mind. And I think cannabis is a particularly interesting example of that genre.

Chris Neff: So, were you working on it to bring new drugs to the market or to develop new technology so that it can be used by people who are in the hospital or how exactly do you translate the work that you do at the Initiative to people who’ve got medical needs?

Professor Iain McGregor: Well it’s a very rich portfolio of activities that we undertake. I think you need to know a little bit about the drug discovery and drug development process to understand the journey that we’re on.

So, if you look at the development say of a new antibiotic or a new anti-depressant or a new cancer drug, often that’s a process that starts with a bunch of chemists looking at a computer screen and modelling the interaction of a particular chemical or a particular target in the brain or body. 

And then it goes through all these different phases of development. You work with cells, you work on refining your molecules, you work on animal models, you do very early stage human trials where you hope that there’s no toxicity of that new drug. 

Then you do your first clinical trials and then you move to large multi-site clinical trials. 

Then if you’re extremely lucky, and often if you’ve spent something like 1.5 billion dollars, you’ll finally get a product that appears on the pharmacist shelf.

So, that process of drug discovery and drug development is incredibly complex.

With cannabis, we have something of a short circuit in that process as much as we have this massive clinical trial that’s been going on for thousands of years where people have used cannabis as a therapeutic. 

And we know that it is relatively safe, that people don’t tend to die as a result of consuming cannabis - there are a few safety concerns – but we can probably accelerate the pace with which we can extract certain chemicals from the cannabis plant and get them into the clinic where they can be useful therapeutics.

Very important to realise that cannabis isn’t just one drug. Within the cannabis plant we have something like 400 different bioactive …

Chris Neff: Wow.

Professor Iain McGregor: … molecules. Most people know THC, which is the one that gets you intoxicated but there’s many, many other cannabinoids. There were 106 last count as well as flavonoids and terpenes and other categories of chemicals. And just about all of them have some sort of therapeutic potential.

What the Lambert Initiative is doing is to try and get a short list of the most promising candidates for a variety of different diseases.

Chris Neff: And what is currently available on the market? What can people access?

Professor Iain McGregor: Nothing (laughs). Just about … I mean …

Chris Neff: Wow.

Professor Iain McGregor: … somewhat of … it’s a flippant response. Within Australia we have a new scheme that’s been introduced by the Federal Government that allows certain categories of patients under certain conditions to access medicinal cannabis products. 

They have followed a model that is really highly restrictive, which means that the scheme has delivered maybe only about 100 prescriptions to individuals. 

It’s incredibly difficult. You need to find not only a GP but also a specialist that will support your application and make quite a detailed application to the Therapeutic Goods Administration to get hold of a particular product. And then you may well have to pay an awful lot of money for that product. 

These products are very expensive relative to the street cannabis that you might source illegally.

Chris Neff: Is there a difference between street-sourced cannabis and medical cannabis?

Professor Iain McGregor: There is indeed. There’s thousands of different strains of cannabis and these different strains have varying levels of cannabinoids and other components.

Your street cannabis is sort of maximising the levels of THC, which is the intoxicating component. So, your typical street cannabis in NSW has about 15 percent THC by weight and so it’s really quite potent in terms of its intoxicating effects.

Some of the therapeutic cannabis products have no THC in them. You don’t necessarily need THC to be present in order to get a therapeutic benefit. And there’s a lot of interest in CBD, which is cannabidiol, as a non-intoxicating therapeutic. Many of the products that are available are high CBD, low THC products.

Chris Neff: So, it’s important for people to know that if they’ve got an illness and they’ve been using street marijuana and it hasn’t been working, that that doesn’t necessarily mean that there is not a cannabinoid treatment that’s available to them, it’s just that they’re using different stuff.

Professor Iain McGregor: That’s exactly right. I mean it’s important also to know that THC itself has quite useful therapeutic properties but only in certain conditions. So, I would rate THC is useful say for nausea, particularly in people who are getting chemotherapy associated with cancer.

THC I think is also quite useful when it comes to pain and I think it’s also useful for sleep as well. But CBD which, is not intoxicating, is useful for anxiety, it’s useful for epilepsy, it’s useful for psychosis. There’s even a THC (sp) lotion that is being developed by a farmer for acne. So, if you’re a pimply teenager, CBD may be the answer.

Chris Neff: Did you just say that there have been 100 total prescriptions?

Professor Iain McGregor: It’s round about 100. I mean this goes up with every month that passes but to put that in some kind of perspective, if you look at Canada, which has had medicinal cannabis available on prescription for many years now, they have about 75,000 patients that access medicinal cannabis. In Israel, they have 25,000 and that’s a country of only eight million people.

The scheme that has been rolled out in Australia, we really only have a handful of people that are currently being given access. And there’s a problem there in that we know that in the community there may be something between 50- and 200,000 patients who are using medicinal cannabis in Australia illegally.

So, you would hope that an enlightened federal system would basically get all of these people off illicit cannabis and onto legal cannabis products. That’s not happening at the moment from what we can tell.

Chris Neff: Is the political situation shifting as community understanding is changing?

Professor Iain McGregor: I think so. I mean … I think what happens inevitably, and this is more a sort of philosophical, political issue. When you have a tension between government policy and what the community wants, that produces dissonance that has to be resolved somehow. It may take months, it may take years, it may take a revolution but it’s inevitable that the community will get what they want.

And I think it’s a very interesting test case of Australian democracy where the overwhelming majority of Australians want compassionate access to medicinal cannabis for people who have intractable pain, who have epilepsy, who have unbearable conditions. Yet the government has rolled out a very tight and risk-averse scheme that is not addressing community demand.

Chris Neff: It sounds like the work that the Lambert Initiative is doing is extraordinary. What are the risks associated with medical marijuana, cannabinoid treatments?

Professor Iain McGregor: It’s a good question and I think it’s important to have a realistic appraisal of the risks of medicinal cannabis. I think we have to think first of all about THC, which is the main intoxicating component. There you have a number of risks, for example there’s memory impairment which is quite well defined, acute memory impairment.

Probably not a good idea to be driving a motor vehicle if you’ve just recently intoxicated yourself with a big dose of THC. 

Having said that, on some parameters, people driving under THC are safer. They tend to leave a larger distance between their vehicle and the one in front but they tend to go a bit slower actually and that’s a dose-dependent effect, the more cannabis they take, the more THC they take, the slower they go. But if an emergency situation arises they’re probably going to be a little bit impaired in their ability to deal with something very suddenly …

Chris Neff:  Mmm hmm.

Professor Iain McGregor: … in terms of their reaction times and decision making.

I think it’s probably not a good idea to give high doses of THC to adolescents when the brain is undergoing a huge amount of development. There’s a bit of a collision between THC and the developing brain that can’t always be beneficial. So, I think it’s an important message for kids to get that you know … every year that you avoid taking high THC cannabis is probably a good year for your brain.

Risks with other cannabinoids for example CBD: there doesn’t seem to be an awful lot of adverse effects. I mean you can take quite a large dose of CBD cannabidiol and you probably wouldn’t even notice it. Then with the other 104 cannabinoids, most of them we think are non-intoxicating but a lot of the research is in its infancy.

I think the safety of most of the components are shown by the fact that cannabis has been consumed for thousands of years. There’s really no recorded cases of cannabis-induced mortality. I think there was a bail of hemp that fell on an Indian dock worker in 1892 and I think that’s the only cannabis-induced death that’s ever been reported.

Chris Neff: It seems to me, and I was reading that you’ve already found some potentially game-changing applications in obesity, dementia, depression. I mean … does the political calculus change as you’re able to address some really problematic illnesses?

Professor Iain McGregor: I think that’s a very good point and it goes to a bigger point, which is that research into cannabis has traditionally been very difficult to do because of the illegal nature of the drug. 

So, you’ve really had to struggle and fill out a mountain of forms to ever be able to run a study, even to give cannabis products to a mouse (laughs,) could be an unbearable process of form filling in order to access cannabinoid. You’d think the stuff was plutonium, not cannabis, it’s been so difficult.

As a result, there’s this kind of evidence gap, which means that a lot of the key clinical studies are yet to be done. 

Cancer’s a great example. We hear stories every week of cancer patients who have been taking cannabis products and show a reduction in tumour size, who feel healthier, who are getting relief from pain, from nausea and so on. But in the case of shrinking cancer cells, there’s not one good human clinical trial that’s been done. It’s almost unbelievable when you hear all the anecdotes, all the stories, some of them quite remarkable.

We had a young woman come to the Lambert Initiative a few weeks ago who recounted a story where she’d been given six weeks to live with an inoperable upper gastro-intestinal tumor and had been given only a few weeks to live. And she started bombarding that tumour with high-THC oil and experienced full remission.

Chris Neff: Wow.

Professor Iain McGregor: I mean the medical profession had given up on her basically and she cured herself. Now we don’t have a large clinical trial featuring you know, 100, 200, 400 patients with the same sort of cancer that’s placebo controlled. We hear this anecdote, we hear these single case studies that are quite remarkable yet the overwhelming clinical gold standard evidence that doctors typically need, is not present.

So, quite rightly in some cases, doctors are extremely cautious and risk averse about encouraging their patients to use cannabis products when that evidence base is not in place.

Cannabis is an outlier, it doesn’t really adhere to the standard pharmaceutical medical model.

Chris Neff: And the more we talk about it the more odd that seems given the variety of things it can treat and what sounds like real positive results that at least anecdotally exist. And I know that people who’ve got multiple sclerosis, which is a very-difficult-to-treat disease, some people aren’t able to use the therapies that are available there have turned to medical marijuana with really successful results. Or at least it’s eased their life and increased their quality of life.

Professor Iain McGregor: Well multiple sclerosis is interesting because it’s something of an outlier in as much as it is one of the few diseases where we actually have quite good evidence and that’s because a UK company called GW Pharmaceuticals developed a cannabis based spray called Sativex specifically for the treatment of spasticity in multiple sclerosis. 

People with MS get very painful muscular spasms and there are some prescription medications that are used for that with varying success but it’s been known for many years that smoking cannabis can be really helpful in that regard and GW pharm took these observations and turned them into a medicine. And there’s been good quality clinical trials around Sativex that show that not only the spasticity but also the pain associated with the MS shows significant relief with cannabis products.

Chris Neff: Is it also true … I read something about the Woolcock Institute. And is that a sleep clinic?

Professor Iain McGregor: It is indeed, yes and we’re about to roll out a study with them to look at how cannabis affects sleep architecture.

So, again there’s a large number of people in the community who are taking cannabis products for insomnia but is there a really high-quality clinical study of the effects of cannabis on sleep architecture? No. There’s a few random observations, there’s a few studies with mice, there’s one study of THC in sleep apnoea that was very positive but only featured a very small number of patients.

So, there’s a real opportunity here to show the effects on quality of sleep. And not just cannabis, remember that cannabis is many different drugs so we can look at different components of the cannabis plant and how they influence sleep and that may lead to a new medication for insomnia that doctors will be relaxed enough to prescribe.

Chris Neff: And just to go down the list one more time on all of the different things that it seems like, ah, medical marijuana can be used for, I also see that children’s epilepsy is one of the areas that has been worked on?

Professor Iain McGregor: I think it’s more a case of what it can’t be used for (laughs).

Chris Neff: Mmm.

Professor Iain McGregor: And I think this goes to a fundamental part of the science that we have here and that is the cannabinoids in the plant interact with your brain and body’s endocannabinoid system and this is one of the most important neuro chemical systems in the brain and the body. It’s involved in just about every physiological process that you can imagine. It’s ubiquitous. It’s in your skin, it’s in your fat cells, it’s in your testes, it’s in your brain, it’s in your ears, it’s everywhere, in your liver.

So, this is a system that doctors don’t learn about yet in medical school because it’s so new our study of the endocannabinoid system, it’s very, very new and the cannabis plant seems to have this special synergy with the brain and body’s endo-cannabinoid system.

So, I would hazard a guess that there isn’t a physiological process that cannabis won’t interact with in some meaningful way and often with a kind of special therapeutic privilege if you like.

Chris Neff: You know … you’re talking about sort of the great potential in research, especially here in Australia, on cannabinoid research. What things are you doing at the Lambert Initiative that sort of … that you’re most excited about in terms of you know … some of these new breakthroughs?

Professor Iain McGregor: Well I think if you go down to the very early stage stuff that we’re doing, we have some quite interesting results of … for example we have a mouse which has the same genetic mutation as a lot of children who have very difficult forms of paediatric epilepsy. These kids can have hundreds of seizures a day and indeed little Katelyn Lambert, who is the granddaughter of our philanthropist, has dravet syndrome, which they’ve treated very successfully with cannabinoid products.

It’s never been clear however what it is in the cannabis plant that is most effective in treating childhood epilepsy. So, the mice that we have that have the same genetic mutation and who have lots of seizures and intellectual disability as well, the mice and social problems too. We can use them to try different components of the cannabis plant and see what’s most effective in controlling their seizures and we have a couple of very exciting leads; components of the plant that haven’t been studied before that are showing quite remarkable anticonvulsant effects.

We’re working, again at very early stage, with mesothelioma, which is a very-difficult-to-treat form of cancer. It’s particularly prevalent in Australia caused by asbestos through so many houses with asbestos. Cladding that were put up decades ago and even short exposure to asbestos can cause this ticking time bomb inside the people where they develop mesothelioma decades later. And it really is a very difficult to treat cancer and quite an excruciating one to suffer as well because people slowly asphyxiate.

We’ve found a couple of cannabinoids here that are producing an incredible toxic effect on the cancer cells. They’re not toxic chemicals to humans but they seem particularly toxic for mesothelioma cells.

We have rats that we give mesothelioma to in order to test therapeutics and normally it’s such an aggressive cancer, these rats don’t live very long and we’ve had some rats that are still alive with mesothelioma as a result of being treated with cannabinoid components. So, that’s very exciting too.

We have an exciting study with humans where we’ve been out in the community talking to families with epileptic children who are using illegal cannabis products to treat their children and we report on their … they report on their experiences, they tell us what life is like using illicit products. Many of them are in fear of being arrested and losing their jobs; it’s adding to the great stress of having a child who has a severe illness.

But in that study, we’re not only learning about their lived experience but we’re also looking at the oils and tinctures and other products that are being used illegally, bringing them back to the lab and analysing them for their cannabinoid content and we’re getting an interesting pattern from that in terms of what types of preparations are being used in the community are effective as anticonvulsants.

We’re at the early planning stages of a study of dementia. People with severe dementia get highly agitated and that’s very difficult to control. Typically, it’s treated with very powerful anti-psychotic drugs that are very sedating and can also cause a lot of mortality and morbidity, these drugs. And we’re working with some top dementia researchers to plan a study around this agitation and psychosis that you get in the elderly.

Chris Neff: Well that’s exciting and it sounds like you’re sort of at the front of ground-breaking research.

Professor Iain McGregor: We hope so. I mean the scientific journey is an interesting one. I mean … if I look back at my own career, not just in cannabinoid research but in all the things I’ve done, the most important thing has been being part of the game.

Chris Neff: Mmm hmm.

Professor Iain McGregor: So, you actually … we pretend that we go into the lab with a hypothesis and we confirm that hypothesis in our experiment. What really happens is that we walk into the lab, we trip over a cat, spill a test tube on top of another liquid and something amazing happens and we’ve got a new cancer drug.

It’s serendipity, it’s chance, it’s random; there is a little bit of planning but all the good stuff I’ve been involved with has happened almost by accident or as if there is some sort of invisible hand that is guiding you that you have very little control over.

So, I don’t want to pretend that this process with cannabinoids is completely logical but what we are doing is rolling out an extraordinary number of different projects and we’ll undoubtedly find out some very interesting stuff, hopefully lead to some new therapeutics that are useful to the community.

But in a way what’s going to be really exciting is the stuff that we don’t expect that we’ll find as we travel through this journey.

Chris Neff: That sounds like there’s lots of projects going on, there’s lots of successes, there’s still a bunch of unknowns but you know … you’ve gotten one of the largest donations in the history of the University of Sydney, 34 million dollars. Is there anything that can stop the progress that you’re making?

Professor Iain McGregor: Well, that’s a very good question and I think it’s important to be realistic about the gift that we were given. It is an enormous amount of money but this is a 10-year plan. Biomedical research by its nature is incredibly expensive and I think I noted earlier that to get a new drug to market as a pharmaceutical, it’s thought to be about one-and-a-half billion-dollar process.

So, we have to be in many ways thrifty. We also have to snowball this money and we continue to fundraise; we were given some money for example recently from the Queensland Government to roll out a study up there, so we’re looking for co-funding opportunities.

Clinical trials … to do a good clinical trial can often be a 5 to 10 million dollar project so you know, in some ways we can only do three big clinical trials with the money that we have so our model is more to seed projects.

So, we’ll go to top clinicians in the dementia field or in youth anxiety and say look, we’d like to work with you to start a clinical trial and we’ll maybe fund the first 30 or 40 participants in that trial but we realise you probably need 200 or 300 …

Chris Neff: Mmm hmm.

Professor Iain McGregor: … participants so we’ll work with you to try and generate other funding. So, in a way what I see the Lambert gift as is a collection of seeds that we can plant in fertile soil here at the University of Sydney and see what grows. But we’re going to need other components, we’re going to need other nutrients coming in, we’re going to need other sources of funding, we’re going to need other brains.

So, we have an incredible opportunity here for seed funding all sorts of different projects but I have to be realistic and say we don’t have all the funding that we need.

Chris Neff: Mmm hmm.

Professor Iain McGregor: We want to attract people to this brand, to cannabinoid therapeutics and encourage other people to give as well.

Chris Neff: Well Iain it sounds like you are providing a hub from which other people can orchestrate and really build on the capacity of Australia to begin treating some of these illnesses and use this research for a positive way.

Professor Iain McGregor: Yes, absolutely. I mean … I think it was an inspired gift from the Lamberts to the University of Sydney. It’s enough money to really make a difference and to attract other people and we’ll snowball that money into something that will hopefully be unstoppable.

Chris Neff: Well that’s extraordinary. Well you’ve certainly given us a lot to think about. Thank you so much for joining us on Open for Discussion, Professor Iain McGregor.

Professor Iain McGregor: Thank you.

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Chris Neff: Thanks for joining us on Open for Discussion. If you’d like to know more about our research, be sure to visit our website piecemakerdesign.com/news.

Next week on Open for Discussion, we talk to Professor Kai Riemer about disruptive technology and the future of work.

You can subscribe to this podcast on iTunes or SoundCloud and you can find me on Twitter @christopherneff.

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