Drug development: from pot to pill

How do we go from a plant - containing hundreds of different active molecules - to a safe drug where the doses can be easily and reproducibly measured out? One company who grow cannabis and turn it into medicines, including a preparation for epilepsy called Epidiolex, is GW Pharmaceuticals. Isabelle Cochrane went to see them...

Stephen - I’m Stephen Wright. I’m Senior Medical Advisor to GW pharmaceuticals having been Chief Medical Officer for the last 14 years.

In 1998, the House of Lords Science and Technology Committee produced a report which started from the observation that people were using cannabis allegedly as a medicine. And they felt that rather than simply clamp down on people who were using cannabis for medicinal purposes, it would be better to see if there is a genuinely medicinal use for cannabis or for components of the cannabis plant. GW was setup at that time specifically to try and meet the requests to determine whether there is genuine medicinal value in the cannabis plant or its components.

Isabelle - It’s not unusual for a medication to originate from a plant. For example, the active component of aspirin is also found in willow trees. But taking a tablet for a headache is clearly quite different from chewing on a piece of willow bark. Similarly, taking a cannabis derived medicine for a complex medical condition is a million miles away from smoking a joint. So how do we get from pot to pill?

Stephen - There are three main pillars of drug development: quality, safety, and efficacy.

The first of them - quality - means can you guarantee that the process you use for producing your medicine produces exactly the same medicine one week as it does another week. When you’re developing medicine based on a plant that is a particular challenge because have many many components, each of which has to be present in the same proportion with every batch that you produce. And it’s a challenge that has to be satisfied not only in the finished product that you produce but also at every stage of it’s production, so the plants we produce have an essentially identical chemical composition from batch to batch, week to week, growth to growth. Of course, within that you have to recognise that in the UK, which is where we grow our plants, cannabis is a schedule 1 drug so everything that we’ve done has been under licence and under inspection by the Home Office.

Isabelle - Once the quality of your drug is assured, meaning you are able to extract it from your plants and manufacture it reliably, the other two pillars Stephen mentioned - safety and efficacy - are determined as with any other pharmaceutical drug in pre-clinical and clinical trials. The end product of this process, in the case of Epidiolex, is pure CBD as a syrup, so you can just pop it on a spoon and swallow it. On the surface of it, sounds like cannabis oil, so is this much different to the various medicinal cannabis preparations you can get on the street?

Stephen - The material that has been seized by police forces around the world are quite demonstrably is more and more and more rich in THC, which is what sought by recreational users. So I think it’s become more difficult to determine what people mean by medicinal marijuana or medicinal cannabis since the plant has been manipulated by growers with a particular aim in mind.

When people have gone through a systematic analysis of cannabis oils and other products sold sort of on the street, what they found is that around half of them contained no cannabinoids at all, let alone the cannabinoids that the claim to contain. I think this emphasises you have to ensure the quality of the medicine that you’re giving to patients otherwise it’s tinkering. You don’t know what you’re doing.

Isabelle - So, perhaps as you might imagine the key difference between a pharmaceutical grown cannabis preparation and the stuff you get on the street is that, in the case of the medicine, you know exactly what’s in it. You’re guaranteed to have the active ingredient in there, but you should also be safe from getting high from your medicine since the levels of THC and CBD, even in the plants themselves are tightly controlled.

But, in the eyes of the regulatory bodies, this does not change the fact that the medication is derived from a plant which is use mainly as a recreational drug…

Stephen - There are certain preconceptions about some medicines that mean the body of evidence you have to produce in order to demonstrate safety and efficacy may be a bit bigger than you might have to produce in other circumstances. And I personally think that medicines based on cannabis do fall into that category.

We are also obliged during development to show whether a drug has a liability for abuse, so are people likely to abuse it? And part of that is does it get diverted away from the patient into the general population? Now it’s very clear, and the Home Office is very comfortable through their advisory body, which is called the Advisory Committee on the Misuse of Drugs, that that has not happened with our cannabis containing medicines, and that’s in marked contrast to some other medicines.

Isabelle - But what does the public think?

Stephen - I think the general public probably has the same preconception that a medicine based on cannabis may get you high. And I think that there has been a duty on us to produce a very substantial body of evidence that it doesn’t. Fortunately, we do have the tools, the measurement techniques, which have enabled us to overcome that particular hurdle.

Isabelle - So what can we expect in the future?

Stephen - There are a lot of cannabinoids, and we believe that a number of them may have therapeutic potential. So what we’ve done, and continue to do is to take out individual components of the plant, or combinations of them, and to explore the therapeutic potential of those individual components or combinations in our preclinical models