Medical uses of marijuana

Why do the chemicals from marijuana affect our brains and are there any medical applications for these compounds?
23 February 2015

Interview with 

Dr Willie Notcutt, James Paget Hospital

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The cannabis growing facility used to create the drug Sativex.

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Sativex Cannabis produces hundreds of chemicals, called cannabinoids, which can affect people in different ways. As well as the well known high, there are other potential medical benefits from these cannabinoids. Dr Willie Notcutt, a pain specialist from James Paget Hospital in Norfolk, took Chris Smith through these chemicals, explaining why chemicals from a plant have such a marked effect on both body and mind...

Willie - Well, there is a range of chemicals there. Perhaps to understand them how they work, we need just to backtrack and think of morphine. Everyone knows about endorphins and talks about endorphins, which are the brain's own morphine-like chemicals. These chemicals lock on to what we call opiate receptors or nerve cells and relieve pain for example. But endorphins are very different chemically from the morphine, which comes from the opium plant. 

Similarly, we have a group of chemicals in the brain and receptors called the endocannabinoids, like endorphins, endocannabinoids. This is a system of chemicals and receptors in the brain, which have a range of effects. But again, endocannabinoids that work in the brain are totally different from the THC and CBD, which are the two of the main chemicals that people know about that come from the marijuana plant.

Chris - And your point being that it just so happens that because the plant makes those chemicals and they bear a resemblance - chemically speaking - to what the brain is using when they're put into the body, they can produce brain altering effects.

Willie - Yes, they mimic just like morphine does. Morphine mimics the endorphins in the brain.

Chris - When they're in the brain, what in fact do those, either the natural compounds, the endocannabinoids or the THC and the CBD you've mentioned coming out of the cannabis plant, what effect do those chemicals have on nerve cells in the brain?

Willie - The two broad effects I think, which we've been studying, the first is, they're rather like a damping mechanism. They damp down pain for example. They're rather like, I would think the sprinkler system in a building. When there's a fire, it breaks out, the sprinkler system comes on. It doesn't necessarily put the fire out but damps it down. I think endocannabinoids and the cannabinoids from the plant do much the same sort of job. But they also have a role in damping down inflammation, both within the nervous system and outside of it as well.

Chris - I was going to ask you, are they active only in the brain or do other parts of the body also have the ability to respond to these chemicals?

Willie - No, the second, outside the body, I mean, there are studies going on into ulcerative colitis and inflammatory condition of the bowel. They've been used in treating the pain of rheumatoid arthritis and found to reflect not only the pain but also, the inflammation that's going on in the various joints that are affected by the condition.

Chris - Have they actually been proper clinical trials or is most of the knowledge about the medical properties and potential medical properties, is that based on largely hearsay and people saying, "Well, I've tried this myself at home in my living room and then I seem to get some relief by using this stuff." What's the situation with that?

Willie - This really led to trials getting underway, was what particularly the patients with multiple sclerosis were telling us. But there's been an extensive programme of proper clinical trials, which have been passed by the MHRA, the home office in London, as being standardised in good quality clinical trials. These have been going on now for 15 years and broadening out now into other areas - and again, based on basic science, there's been basic science onto these compounds going on now for 40 to 50 years. And they, and almost the clinical research can't keep up with what is coming out of the basic science labs and similar sorts of research.

Chris - How are doctors seeking to administer the agent because obviously, one doesn't want to be encouraging people to smoke this stuff? So, there must be safer ways to administer the agent.

Willie -  Yes. This was a major challenge in the late '90s, was to develop extracts of cannabis that were of medicinal quality. The first was to standardise the amount of THC and CBD that we were going to be using. And so, it needed to be extracted from the plant so that there were no impurities. And then we had to have a delivery system. The one that we've been currently using principally spraying it under the tongue so it's absorbed through the lining of the mouth. We had to prove in the clinical trials that this was safe to do it and didn't produce the sorts of psychosis that you're going to be talking about later. Most of all of course, that it was going to be effective for patients. That patients were going to get benefit from it and actually, prove by clinical trial, what people have described for many, many years as anecdotes about their own experiences, now to prove it. so, we can say: "here is a proven medicine that can be used and can be applied in different ways."

Chris - Apart from the conditions you've mentioned, ulcerative colitis in the intestine. Multiple sclerosis and some pain states, what other conditions might be amenable and treatable using these sorts of chemicals - THC and CBD?

Willie - Well, there's a huge range of - if I just stick on pain - there's a huge range of pain states that don't have treatments for them or have insufficient treatment out there. But there's been some work in diabetes, psychosis. There are some new, very exciting work going on with the agent, cannabidiol or CBD, which really has no effect, no psychoactive effect on the brain in terms of like the high of THC. But there's work going on with that in the treatment of childhood epilepsy and some very exciting results being seen of people who, of children who have continuous fits and then been given the agent, are given CBD and finding that the fits are totally controlled. So, there's a range of things going on. There's also work on, consideration of work on autism, even there's some work going on possibly or into Alzheimer's disease because we know that the cannabinoids are protective and protect against inflammation, particularly within the brain. So, there's a huge range of exciting possibilities out there to be researched into.

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