Psychedelics In Medicine

Last week, the ocean caught fire. Twice. That’s not something you can say everyday. Firstly, the Gulf of Mexico hosted a glowing ‘eye of fire’ not far from an offshore oil rig; then, just two days later and on the opposite side of the world, a massive fireball erupted from the Caspian Sea, creating a column of fire that could easily be seen from 45 miles away. Sally Le Page spoke to geologist Mark Tingay from the University of Adelaide to find out what actually happened…

Mark - There was a leak in a gas pipeline near one of the major oil and gas fields in the Gulf of Mexico. That causes a lot of gas, obviously, to leak out of the pipeline, and lightning ignited that bubbling gas and caused the big eye of flame that we all saw on social media.

Sally - It did look incredibly dramatic. It didn't even look real to be perfectly honest with you.

Mark - It was incredible. And yeah, it is something that unfortunately we do see occur whenever we have a major fire associated with a major hydrocarbon leak in oil and gas fields.

Sally - How can an ocean catch fire? It's surrounded by water, water puts out fire, doesn't it?

Mark - Yeah, that's what you'd think isn't it? The water should put out a fire. In reality, it's not the water that's on fire, it is just the gas. So all the bubbles of gas, all the methane, natural gas, that's coming out of the ground, bubbles up through the water. And then once it gets to the surface, it's essentially feeding that fire. But the water itself actually isn't on fire. It just looks like it.

Sally - The images from that were, for me, it seemed like a kind of once in a lifetime sort of image, but then it happened again! We had a second fire in the oceans, this time in the Caspian Sea. What happened there was it the same deal?

Mark - The fire in the Gulf of Mexico was a broken gas pipeline near an oil platform. The fire in the Caspian Sea was actually a perfectly natural event where we had a big fireball that jetted out from the eruption of a major mud volcano on a very small island in the Caspian sea.

Sally - Wow. I've never even heard of a mud volcano before. What is a mud volcano?

Mark - So a mud volcano is a part of the Earth where subsurface water and mud essentially come out of the ground. So if you think about a volcano, a normal volcano, those erupt molten rock and ash. A mud volcano is a bit like that, but it erupts watery mud. And along with it, it can also erupt a lot of gas.

Sally - How big are they? Do they look like the mountains that we think of when we think of a volcano?

Mark - Most of them in the world are very small things that might only be tens of metres in size. The ones in Azerbaijan are quite unusual in that they do look like real volcanoes. They can be hundreds of meters tall.

Sally - So you've got this liquid mud, you've got these bubbles of natural gas erupting. What then sets that off to create what was such a dramatic mushroom cloud going into the sky of fire?

Mark - We're not a hundred percent sure because of course it's not something that we can easily test, but there's two main ideas. One is that it's just a very sharp drop in pressure. There's been a lot of simulation that suggests that just the very sharp drop in pressure could be enough to ignite the gas on its own. But I think another possibly quite likely situation is that when you've got all this very violent eruption of mud, it's not just water and clay. It's got boulders inside; rocks, cobbles, big chunks that can be half the size of a car. And these are things that are being violently thrown into the air. And of course they can bang together and potentially cause a spark. And you really just need one spark to ignite that huge amount of gas.

Sally - So this is the natural equivalent of striking two flints together.

Mark - That's right. Yes.

Sally - What are the environmental consequences of these fires happening in these oceans?

Mark - It's a good question, and I'm not exactly sure what the consequences are going to be of, for example, the Pemex fire. If it's mostly gas, then most of the gas would have burnt. And so your biggest issue there is of course, the emissions and its contribution to climate change. The real concern would have been how much gas might've been dissolved in the seawater. And if there was any oil that also was released, which of course we know from oil spills can cause huge devastation over a large area. Pemex has denied that there was any environmental damage or major oil spill. From mud volcanoes, of course, it's a natural phenomenon. They do happen quite regularly in that part of the world. They do erupt quite a lot of oil. They can erupt quite a lot of gas. I haven't heard of any oil spills visible from the mud eruption in the Caspian. The impact on the environment there is probably quite minimal, and of course it's a natural event. But mud volcanoes do contribute significantly to Earth's natural methane budget, that of course we take into account when we're looking at the impact on the climate cycle.

There have been reports that kids have been using soft drinks to fake their COVID tests and get out of school. In fact, you can find out how to do it on TikTok, and apparently all you need is some orange juice or cola. But is it true? And if it is true, how does it work? Eva Higginbotham spoke to Mark Lorch from the University of Hull...

Eva - Many of us are familiar with lateral flow tests by now - the small plastic COVID tests that we can do rapidly at home, but fewer of us actually know how they work - myself included. I didn't know that they even have gold in them… How much money do you think I could make if I collect all the lateral flow tests I can find and take the gold out?

Mark - Uh, pennies, probably! That's a really good question. You know what? I might have to go and do the calculation to figure out...

Eva - That's chemist Mark Lorch from the University of Hull, and when he heard reports about people faking positive lateral flow tests using various soft drinks, he took it upon himself to figure out how on earth this works. But first, here’s how lateral flow tests are supposed to work...

After swabbing the back of your throat and nose and mixing the swab with a little buffer solution, you put a drop of the solution onto the sample window, otherwise known as S window, of the test. This liquid gets pulled along this absorbent strip of material inside the test, and along the way, will be exposed to specialised antibodies. Now, your immune system makes antibodies, these protein molecules that are highly specific in what they will bind to, in reaction to foreign invaders in your body, but scientists can also engineer antibodies to bind to whatever they like, and can stick colourful chemicals onto them too. So in this case, they made some antibodies that are highly specific to the coronavirus and are bound to little nanoparticles of gold which, surprisingly, look more purple and reddish than what we think of gold. If your sample contains coronavirus particles then those colourful antibodies will bind to the virus particles. These then get stuck to a second set of antibodies halfway up the test, at the T or Test window, which is why you would see a reddish-purple line there if you’ve tested positive. There’s a third set of antibodies involved too, stuck at the C or control line - these antibodies will bind to the other antibodies used in the test, and are put there to show you that the test has worked. If you get a control line and no test line, you have a negative test. If you have a control line and a test line, you have a positive test. But there are reports of kids faking positive tests using soft drinks. I wanted to see it for myself, so got Mark to talk me through it...

Okay. So I've got myself some orange juice. Unfortunately, it's got bits in, is this going to be a problem?

Mark - I don't know actually, I've never tested this with orange juice with bits in! So this is groundbreaking science going on here. Do you get an apparently positive result on a lateral flow test if you use orange juice with bits in?

Eva - Let's find out! All right. So I'm going to squeeze a couple of drops then onto the sample window just as I would if I was taking it myself. And I haven't mixed this with the buffer solution, this is just straight-up orange juice

Mark - What's happening now then is that orange juice is wicking up the device, it's picking up the red nano-particles attached to the antibody and it's carrying on the lateral flow test

Eva - And I can see a line where the T is! And it's actually, it's getting stronger as the seconds go by. It's just past the C now, and it's getting stronger there too. So there you go!

Mark - Well, there we go, you heard it here first - orange juice with bits in does give you a fake positive lateral flow test result for COVID

Eva - Right. So what is going on? Why does this happen?

Mark - Good question. Now, the thing that I've noticed is that all of the fluids that create this fake positive result are all acidic. So colas, orange juice, and so on, all have are about pH 3 and 4, so they're quite acidic solutions. Now the antibodies have evolved to work in very different conditions, they work in your bloodstream, which is about pH 7.3, so almost neutral, and the acidity of these drinks and so on is then quite an alien environment to the antibodies. Now antibodies are proteins and proteins are really quite sensitive to the conditions around them, particularly the pH, and by putting the antibodies in acidic conditions what essentially is happening is you're starting to unfold the antibodies. So antibodies, like all proteins, are long chain-like molecules that fold up into a very well-defined shape to do their job correctly. And when you put them in acidic conditions, you cause the antibodies to unfold slightly, which essentially destroys the specificity of the antibodies for the virus instead makes them stick to all sorts of other things in the solution, most obviously the gold nanoparticles and that's what results then in that line at the T.

Eva - So there you go - it comes down to the fact that antibodies often have quite a specific pH range that they operate at, much like how the enzymes in your stomach that help breakdown food work best in an acidic environment. And what if you want to check if a positive test is real or not? Mark told me that you can let it dry out over a few hours and then add some buffer solution to the sample window. This will wick up the test and, over time, reset the pH to about neutral causing the antibodies to get back into their proper shape. If the test is fake, the T line will disappear, and you'll know to start keeping a closer eye on the orange juice in your fridge.

It’s time for the mailbox - the part of the show where Sally Le Page and Phil Sansom respond to listener messages...

Sally - This week listener Geoff emailed us saying that he’s been double COVID jabbed, but started getting hayfever symptoms like coughing, sneezing and runny eyes. He subsequently took a couple of lateral flow tests - the first one was negative, but the later one was positive for COVID. This aligns with broadcaster Andrew Marr’s experience - he also had cold-like COVID symptoms after being doubled jabbed - so this all goes to show that if you've had both vaccine doses and you catch COVID again, the symptoms might not be the one you're expecting.

Phil - Geoff, your observation is backed up by evidence from the ZOE symptom tracker app. They say the top most common symptoms for those who’ve had both doses are now a headache, a runny nose, sneezing, a sore throat, and loss of smell. A cough and a fever are now a good way further down the list. This isn’t 100% conclusive evidence, and the symptom tracker app obviously isn’t catching everyone, but something to watch out for.

Almost all psychedelic drugs, even if they’re synthesised in a lab, are based on products found in nature. The question then is - why does nature produce compounds that make you see colours and feel at one with the universe? That’s what an American team set out to answer when they looked into how magic mushrooms have evolved. Hannah Reynolds from Western Connecticut State University told Eva Higginbotham how they did it…

Hannah - There's actually over 200 species of magic mushrooms, and they're scattered all over the world. A lot of them aren't even very closely related to each other. And we were looking to understand - what are the genes that actually make the psychedelic compound psilocybin? And then we wanted to understand - how did these genes evolve?

Eva - And how do they make that psilocybin?

Hannah - So what they're starting with is the amino acid tryptophan. And this is what, if you eat a lot of turkey at the holidays, this is the thing that people say makes you sleepy. It's been debated whether it's just having a giant meal makes you sleepy or if it's really tryptophan... but they start with tryptophan, and then they do basically five chemical transformations, and each of the steps needs a different gene. So those were the genes that we were searching for.

Eva - And how did you go about looking for them?

Hannah - So what we did is we took six mushrooms - three were psilocybin producers, and three were not - and we did genome sequencing of all six. And then what we were looking for is: what are the genes that are shared just between the three magic mushrooms and not the others? That left us with a fairly small pool of genes, because we were ignoring the genes that were just essential for a cell to survive and to grow. And once we had that pool, we looked for the functions, and we basically found this gene cluster. And they also were close to each other on the chromosome.

Eva - How do you know that these genes that you found are the ones that make psilocybin? How can you test that?

Hannah - Great question. So what we did is take the gene sequence and then get the protein from it, and then gave it tryptophan, and it made the product that we expected. We in the United States had to stop there because of regulations that... at the time we were not allowed to create - I think they're called - class 1 drugs. But another team independently found the same genes in a different genome of mushrooms, and they were able to take these enzymes and make psilocybin from them.

Eva - And so the fact that all of these genes were clustered together in the same place of the genome of the mushroom - can we learn anything from that about how those genes might've evolved?

Hannah - Yes. In fungi, when we see that kind of pattern, sometimes that's associated with a history of horizontal gene transfer - gene jumping, if you will.

Eva - I see. So it's not like all the mushrooms across the world all independently were like, "you know what? Let's make some psilocybin." It's more like mushrooms that were next to each other shared the genes required to make psilocybin, and through that mechanism, it spread.

Hannah - Yes. So that was our final step to our paper - looking at what might those environments have been. And the environments that magic mushrooms are usually found in are dung, decaying wood, and mutualistic associations between fungi and tree roots. And it looked like the dung environment was where a lot of these exchanges might've happened.

Eva - And what is the point of these mushrooms making the psilocybin in the first place? What benefit do they get from it?

Hannah - What we think is that, in the environments where the magic mushrooms are growing, they are having to deal with insects, especially insect larvae - that are eating the decaying wood, that are eating the dung, and that maybe even are eating them, especially as they're growing through that resource before they actually make the mushroom itself. So we think that making these hallucinogenic compounds may slow down the insect enough that the mushrooms have a better chance of colonising that material, and actually growing and making a mature mushroom.

Eva - So it's about competition.

Hannah - That's our take on it.

Eva - And what does it do to an insect? If an insect eats a magic mushroom, is it going to get high? Are they like hippies?

Hannah - I think they do. What it feels like to them, I don't know, but I suspect that their brains aren't that different from ours in terms of what this does. Of course insects are living in a more smell-based world than a visual-based world. So I can only speculate, but I would think if they hallucinate, they're not so much getting visuals as maybe olfactory confusion.

Eva - That's amazing!

Hannah - That's a wild guess.

Eva - Smelling hallucinations!

Hannah - And how would I even test something like that? I have no idea. But that's what I imagine.

In Bristol, a company called Awakn Life Sciences is trialling the use of MDMA to treat addiction. MDMA isn’t a classical psychedelic drug - in fact, as a rave drug it’s also known as ecstasy - but as psychiatrist Ben Sessa told Phil Sansom, in the clinic it has some very useful psychedelic properties...

Ben - It has an amazing capacity to induce a state of empathy, and to turn off the fear response. Now this is very important with people who have trauma related disorders, particularly addictions, post-traumatic stress disorder... it's very difficult for people to do therapy with these disorders because the trauma is so intense. They can't recall the painful memories without wishing to flee and end the treatment. MDMA has a remarkable quality to turn off the fear, and allow you this brief few hours in which to carry out trauma-focused psychotherapy.

Phil - Interesting. So you can still remember what you're thinking about, but you don't feel afraid.

Ben - Absolutely. It's quite pharmacologically unique, MDMA, in that it just turns off the fear response whilst leaving the other faculties intact.

Phil - Based on the study that you've done - how well does it actually work?

Ben - It was what we call an open-label pilot study, and we need to do some randomised control studies to further that research, but the outcomes were very positive indeed. With the control group around 75% of people at nine months had returned to pre-detox levels of drinking, compared to just 20% in those that underwent our MDMA therapy.

Phil - That does sound like a big change. What's the link though between trauma, which MDMA is helping people access, and alcoholism?

Ben - There so often is trauma, particularly childhood trauma, abuse, and maltreatment, that emerges very early in life and causes disruption to a person's attachment relationship. Now the attachment relationship is the blueprint for our psychological functioning throughout life. It's very well-known that damage to attachment relationships is associated with most, if not all, chronic mental disorders. So it's no surprise that those patients who become addicted to drugs of all kinds so often have these difficult childhoods and poor attachment relationships.

Phil - So is it as simple in your studies as, you give people a pill and then they feel better? Because I think people are quite wary about the idea that you can solve a mental health problem that's got so many different causes with a single drug.

Ben - Absolutely. I think the interesting thing about psychedelic research in general is this is the antithesis of the way we currently use drugs in psychiatry. Most mental health medications one takes on a daily basis for weeks, months, decades, in order to mask symptoms. The interesting thing about psychedelic-assisted psychotherapy is you only need to take the drug on a few occasions mixed with psychotherapy, and that's where it really works.

Phil - Oh, so it's 'talk talk talk talk', 'drug', 'talk talk talk talk talk'.

Ben - Yes, the bulk of the work is done in the non-drug post integration sessions.

Phil - You rarely get a one size fits all medicine in the field. So how many people does this actually seem to work for?

Ben - Well the results of psychedelic research of the last 15 years have been staggeringly good for a range of different compounds - psilocybin, ketamine, MDMA - across a wide range of psychiatric disorders including addictions, anxiety disorders, depression. So it remains to be seen how well psychedelics could be used in psychiatry, but so far the results suggest that the applications could be very wide indeed across multiple disorders. Indeed, we may one day look back and think, "why did we ever do psychotherapy without drug assistance with psychedelics?"

Phil - You really think it's that big of a deal?

Ben - We have to be very careful not to get ahead of ourselves here. One of the reasons this research died in the 60s was because there was too much of a messianic approach that these drugs were panaceas. They're not panaceas. Mental health is complex. There's psychological factors, social factors, as well as biological and genetic factors. But it certainly seems looking at the results of the last 15 years that the results are extremely good indeed.

Phil - Where do you think this is going then Ben? Am I going to be able to go to my GP and they prescribe me some MDMA?

Ben - If the research continues at the pace it's going, then we should see MDMA approved as a drug to treat trauma-based disorders in around 2023. Psilocybin, a couple of years after that. Ketamine is already available for the treatment of these disorders. One of the big goals we have is to make sure that this appears on the public health service. It's no good if it's just confined to private medicine. So we need to work with the regulatory authorities and with the funding authorities to make sure that this is free, public access healthcare for everyone.