Dr (No) Pain

So how did you end up in cannabis?

I’m a surgeon by training. One day a week, I do operations on complex cancers of the pancreas and liver. The natural extension to that clinical interest was research around (pancreatic) cancer biology. In 2018, the Nobel Prize was awarded for cancer immunotherapy and we suddenly realized we’d been barking up the wrong tree. The real prize in the treatment of cancer is to focus not on the cancer cells, but on the immune system.

After that, I became involved with looking at ways we can modulate the immune system, which is how I stumbled across CBD – a very effective anti-inflammatory. At the time, it hadn’t been mapped out on a scientific level in relation to cancer biology. We could see the therapeutic benefit in combining CBD with cytotoxic chemotherapies for pancreatic cancer – we just didn’t know how. It was a black box. Eventually, we secured funding for the Imperial College Medical Cannabis Research Group, which I now lead. 

As well as cancer biology, we research another of my clinical interests: pain. As a surgeon, I unfortunately cause people pain by default – a short-term disadvantage we try to address in surgery. We’ve been trying to move away from systemic opioids, which have negative effects on respiratory function and predispose patients to chest infections, ultimately keeping them in hospital longer. Cannabis is a promising alternative. 

Where does Sapphire Medical Clinics come into this?

My colleagues and I set up Sapphire Medical Clinics around the time the law changed, almost as an extension of our research. Having established what cannabis can (and can’t) do naturally leads to one of two things: either conducting clinical trials for marked authorization or prescribing medicines under certain circumstances off-label. We saw a really interesting opportunity in collecting that data so that we could help eliminate the medical cannabis knowledge gap and, ultimately, allow more people to access these medicines for free on the NHS.

Is it frustrating to know that medical cannabis is legal, but still so difficult to access?

It’s heartbreaking to see patients who obviously derive great benefit from the medications, but can’t access them for free like other treatments on the NHS. But at the same time, I can see how it has happened. We have a system in place in the UK in which we undertake cost-effectiveness analysis to establish whether taxpayers are prepared to foot the bill on a population level for certain medicines. I don’t think cannabis should be treated any differently. 

But these patients have already been treated and found to benefit from cannabis – so even if we wanted to put them in a trial, it would be unethical to randomize them. NHS England conducted a review of what they call “Barriers to accessing cannabis-based products for medicinal use on NHS prescription” in 2019. One of the recommendations was to set up an alternative study design to record data in a meaningful way. We urgently need randomized controlled trials so that we can get high-level evidence. Had those recommendations been acted upon, something would already be in place today.

What’s your views on other countries’ approaches to access to medical cannabis?

Last year, Sapphire established a protocol to help the NHS with data collection. We even met with health secretary Matt Hancock, who seemed interested in understanding the access issues. Then, of course, COVID-19 placed everything on the policy side on the back burner. But I hope they’ll revisit it soon. It’s heartbreaking to see patients spending so much money on medicine when we have an NHS England recommendation for dealing with this issue that hasn’t been implemented. I think the type of healthcare system we have is at the center of the difference. The US, for example, is primarily a private healthcare market. We’re a social healthcare system and, because of that, there are huge differences in how medical cannabis has – and will – be implemented. The incentives are different.

If we want medicines for patients on the NHS, we need robust data showing that the medicines are cost-effective. If you want large numbers of patients to access these medicines in the US, you don’t necessarily need to take the same route, which is why there are disparities in access to medical cannabis.

Is there anything we can learn from the US?

The data they’ve collected give an indication as to how certain medicines may affect subgroups of patients, but that’s where the similarities end. There is limited overlap in the ways we go about more robust data collection. The UK will inevitably go down the familiar drug development route with randomized controlled trials across multiple indications. The question is: what do we do in the meantime? In 20 years, we will have a bunch of market-authorized medicines – but right now, we have medicines that are not yet licensed for most indications and large volumes of patients seeking access to these medications.

We know that a large number of patients in the UK (1.4 million according to a YouGov poll) self-medicate on the illicit market to treat a medically diagnosed condition, which I imagine is reflective of most countries in the Western world. What do we do in this intervening period? Though these are mostly policy decisions, we have a responsibility to accelerate the progress we’re making as a scientific community. Clinical data goes hand in hand with sensible policy that ensures we’re not denying patients beneficial treatment. At the same time, we have to make sure that medical and non-medical applications aren’t confused. There must be a robust system to evaluate patients. Regulators in the UK are also encouraging data collection on patients who are treated. Although individual countries in Europe have different mechanisms to deal with this, I think the end goal is going to look very similar.

Cannabis is a very politicized topic in the US. Is our lack of public discourse in the UK limiting us?

I don’t think so. Our primary focus in the UK is to show through data that this is a medicine like any other. That battle is largely won; I don’t know any doctor who would argue with cannabis as medicine. A high proportion of people favor legalization of medical cannabis. The problem with the US is that there is this confounding issue of adult recreational use, which is entirely unhelpful when it comes to discussion of medical use. We haven’t argued that debate in the UK, which is good, because we need a few years to get a clear view of what’s good for people’s health. Only then can we have a discussion about recreational use.

What are the barriers to getting data on this scale? 

Funding is obviously key. We need everyone – policymakers, regulators, medical professionals, academics – to sing from the same hymn sheet to work out these compounds’ medical uses. That requires short-term solutions. One of the positive things in the UK is that NIHR, a major funding body, has designated calls for research into cannabis-based medicines, which means they have funds reserved for this kind of research. Despite that, we haven’t seen any large-scale randomized controlled trials, in part because they are so expensive. We need to prioritize and accelerate this, because we urgently need to resolve the mismatch between our knowledge and patients seeking treatment.

Why hasn’t it happened yet?

It goes without saying that the pandemic has slowed things down. Clinical research was essentially put on hold for a year. But a group effort almost certainly requires national infrastructure. Hopefully, in this post-Brexit era, more resources at a government level will be dedicated to these kinds of initiatives between industry and academia.

Do you think the rise in popularity of CBD is helping or hindering medical cannabis advocacy efforts?

A bit of both. It’s certainly not helpful to read tabloid articles claiming that CBD cures everything under the sun (because it doesn’t), but it clearly highlights the fact that we need to understand CBD better.

The UK’s buoyant wellness sector may cloud perceptions on CBD’s medicinal uses, with public perception distorted by the fact that not only can a doctor prescribe CBD, but you can also buy it on the high street. So is it a medicine or not?

Is 20 years a realistic timeframe for us to start seeing approvals?

I imagine they will come in dribs and drabs, like we’ve already seen in childhood epilepsy syndromes. The first approvals will most likely be for orphan diseases, because they are easier from a regulatory point of view; treatments that require big trials, such as pain, will come later. It will be a gradual process but, in 20 years, we’ll have fewer unlicensed medicines prescribed to patients simply because we will have gone through this process for many of the indications that may benefit from medical cannabis treatment.

Can you tell us more about your own research activities?

We’re doing some really interesting work on pain, essentially trying to untangle the spaghetti of different compounds present in the plant. Right now, we’re looking at three individual cannabinoids and seeing how, when combined in different proportions and doses, they create an analgesic effect (or not).

Believe it or not, even studying those three is incredibly complicated. Those cannabinoids alone could result in many different permutations. Now, say you were to look at 120 cannabinoids (forget about terpenes or anything else); the resulting number of permutations could fill an entire slide. You quickly understand that it’s an impossible research project. That’s why we simplified it. Once we understand those three cannabinoids, we’ll add in more.

So far, we’ve been able to decrease the dose of THC by adding another cannabinoid without reducing the analgesic effect in vitro. I’m excited to develop that research further, and hopefully translate it to human studies soon.

If you weren’t doing this, what would you be doing?

I’d be involved in drug development for cancer with immunotherapies. I still hope that I will someday cure cancer – but, although there are lots of people working on immunotherapy at the moment, there are far fewer looking to plug the gaps in our understanding of medical cannabis.