Can I hack my hormones to improve my mood?

Do happy hormones exist? Is there a chemical recipe for improving your mood and is oxytocin really the biological basis of love?

Hormones: The Inside Story

Episode 12 – Can I hack my hormones to improve my mood?

It’s time for the final episode of the series. And I know your first instinct on hearing that might be to weep bitterly, but hold off- because this time on Hormones: The Inside Story we are looking into HAPPINESS.

Mood is a complicated little pickle - obviously there are tonnes of external factors that can cheer us up - or these last two years more likely make us miserable - but - on the inside - is there a hormonal recipe for happiness? Can certain actions or drugs ever bring us straight to our happy place and help keep us there?

Well, that’s what we’re going to be finding out - and - seeing as this is an area of popular science with a whole bunch of nonsense attached to it, we’re going to try to sort fact from fiction while we’re here.

Cathy: So we know that for mood disorders like anxiety and depression, the role of chemical transmission in the brain is really important in terms of regulating our mood. And so I've had a long standing interest, of course, in neurotransmitter systems, but also in hormones, because we know the hormones play a really important role as well in regulating our moods as well as our general physiology.

Georgia: This is Professor Cathy Fernandes, from the Institute of Psychiatry, Psychology and Neuroscience, which is part of King's College London. Now before we get to things like the cuddle chemicals and happy hormones you might have heard about in the media, there’s something we need to get out the way about hormones and their close relatives, neurotransmitters.

Cathy: Both neurotransmitters and hormones are what we consider chemical signalling molecules. The difference between them is really where they act and how specific their release is. So with neurotransmitters, we think of those as being chemical messengers that transmit a signal from a specific part, something called a neurone to another part of the neuronal system, the synapse, which is usually on a target cell. So this is usually something that's very specifically released and controlled over short distances, relatively speaking, within the neuronal system. That could be the central nervous system in the brain or the peripheral nervous system, because we also have nerves outside of the brain, too. With hormones, this is where it's much more a longer distance that's covered. So we think of hormones as being any kind of chemical messengers that are transported to kind of distant organs rather than being in a very focussed, specific release. So that's essentially the difference. They both are important in signalling information, it’s just the distance they cover. Neurotransmitters are shorter and hormones are larger distances in our body.

Georgia:  So does that mean when often we're talking about the hormones of happiness, people are actually referring to neurotransmitters?

Cathy: I think so, because, we know that mood is regulated and controlled within the brain. But having said that, we know that the brain and the rest of the brain do communicate with each other and there's a very important balance dynamic that occurs. So our overall physical health does relate to our mental health as well. So I think it's important to not forget about the periphery. So although we know it's the brain that's the driving force, of course, the driving organ, if you like, that controls and regulates mood, it does receive inputs and signals. And it's a two way system going out from the brain as well that goes out to the rest of our body. And so we know that the brain talks to the rest of the body and that there's also a two way communication.

Georgia: Hopefully you'll forgive me for sneaking all this talk of neurotransmitters into an endocrinology podcast, because deep down they’re all part of the same puzzle, and they all tend to get referred to as hormones most the time anyway. So I asked Cathy to take me through some of the most well-known mood molecules. First on the list...

SEROTONIN

Cathy: So serotonin or 5-Hydroxytryptamine, or 5-HT. Serotonin is really important in regulating our mood, particularly things like anxiety - it plays a very important role in depression as well and many of the drug treatments that target and the antidepressants target depression alter the levels of serotonin in the brain. I mean, it's only one of the few monoamines, as we refer to them, because chemically they're related that play an important role.

Georgia: Is it the case that you can boost your serotonin with them with some kind of everyday activity, or is it a bit more complicated than that?

Cathy: I mean, it's potentially a bit more complicated than that. But we do know there are very important lifestyle activities that do influence our mood and do probably result in changes in the brain. So these are probably no surprise, really but things like making sure you get enough sleep, eating well and exercise, these are all already important lifestyle activities that can really support brain activity. Because as I mentioned before, the brain is an organ that needs to be looked after. It needs oxygen, these nutrients. It needs to have rest as well from its activities so that these are all important activities that can help boost overall brain function. Whether those specific activities alter serotonin specifically or whether it's probably more complex than that, because it's not just serotonin, of course, in the brain.

Georgia: Next up…

Dopamine

Cathy: Dopamine plays an important role in mood, but it's probably most famously known for its role in reward and signalling reward mechanisms in the brain and whether this is a reward to typical daily activities. I mean, this is one of the reasons that our brain makes sure that we do sleep, that we do eat, that we do engage in various activities. And of course, it's also the system that then is targeted by addictive drugs, for example, because that's how they kind of signal their rewarding properties because they activate dopamine in the brain. So we know that dopamine plays an important role in reward, but it also does play a role in mood. So we know that some antidepressants do also target dopamine as well as serotonin so we know it can play a role in mood too.

Georgia: So dopamine is important in things like learning and reward, but it’s not necessarily that increasing dopamine is good for you because it's associated with problematic and addictive behaviour.

Cathy: Exactly. And I think that brings up a really good point about it's unfortunately not as simple as too much or too little if any of these chemicals in the brain or hormones in the body. So the whole kind of physiology, which is what regulates our body, so, for example, increase some other particular neurotransmitter, the body is going to work hard to counter that effect and it can over counter it so it can actually result in the opposite of what you want to try to increase dopamine your system might work so hard to maintain the balance, you end up reducing the effect of doping. So it's about this kind of very careful balance that happens in the body. So it's very hard to just increase or decrease the amount of transmitters and have a good result. So you can do it. But it usually ends up tipping the balance too much the other way, because the body is working like a very finely tuned system and taking a drug, for example, is like throwing a bucket of water over that finely tuned system. It's a bucket of chemicals because in the brain we have very tiny amounts of chemical of these neurotransmitters being released and released in this controlled fashion, particularly in the brain. So that's why it's very hard to use drug treatments to kind of alter these levels.

Georgia: And I suppose one person's depression and another person's depression might be caused by very, very different things in the brain.

Cathy: Exactly. So we know there's a huge amount of individual difference in how our systems are set, everything is on a spectrum.

Georgia: Next, let’s give it up for...

ENDORPHINS

Cathy: So that's another good example of something which probably relates more to sort of the reward system and thinking about stimulating that kind of excitement, that kind of high that you might get. And whether that's happiness, I guess, is debatable. But again, endorphins can be released by things like exercise, for example, and these can definitely influence mood results in this sort of more kind of, you know, perhaps excited hyper kind of states that for some people they find them rewarding and therefore makes them feel happy. Often, you know, the endorphins, it's kind of a short term effect that occurs. So, again, these are different class of chemicals that work in the brain so having kind of sustained the kind of long lasting effect on mood doesn't really occur with endorphins. And, you know, there are lots of kind of recent reports of not just exercise, but things like cold water, swimming, for example, that also trigger endorphins and that and it could be that sort of repeating those activities can continue to kind of give you those mood elevating effects.

Georgia: And last but by no means least, the infamous ‘cuddle chemical’ itself…

OXYTOCIN

Cathy: Yes, oxytocin, the love hormone, I think it often gets referred to. So we know that oxytocin has been around for a long time in terms of understanding its role in physiology and how it relates to various functions and the reproductive system. For example, we know it's really important during pregnancy. It's important for milk letting down. So for breastfeeding, we know that oxytocin increases at that time and it's been thought to play really important role in kind of establishing bonding between mother and child, for example. So I think for a long time, people have wondered about the role of oxytocin in terms of regulating moods, particularly around social interactions and social behaviour.

Georgia: Oxytocin has been a hot topic in the hormone world for the last few years. It supposedly spikes when we fall in love - or just enjoy some sexy times - it’s released when we gaze into our dog’s eyes, and it’s even supposed to surge en masse at weddings. In fact, you can even buy celebratory champagne flutes engraved with the chemical formula of oxytocin, for your big fat geek wedding.

Reading all these stories, you’d certainly be forgiven for thinking that oxytocin truly is some kind of wonderful love drug. But what’s science fact, and what’s science fantasy?

It’s time to ask someone who’s spent many years looking into this little chemical with a big reputation.

Gareth: Oxytocin is a lovely hormone, it’s been a kind of long love of mine, really since when I started out back in 1977.

Georgia: This is Gareth Leng, a recently retired neuroendocrinologist and author of ‘Heart of the Brain’.

Oxytocin, as we just heard - is important for birth and lactation - so pretty important for a species survival. But ideas about oxytocin's importance go much further

Gareth: It's involved in sexual arousal and sexual behaviour, in males it’s involved in the presence of erection, in females also sexual activity is controlled by oxytocin in many species. It’s got another role in appetite. And the more we look into it, the more we realise that there are lots more functions of oxytocin in both the brain and the better and the periphery.

Georgia: It’s a real multitasker, but, especially in the media, it's called the cuddle chemical, so it seems to be exciting people for their particular roles in terms of the way we bond and where we want to socialise.

Gareth: That’s true, the first hints for that came in the 1970s. These studies were done in a species called the prairie vole. Now, most mammalian species are not monogamous. Humans are an exception in that they're one of about three percent mammalian species which do show pair bonding, that's a long term exclusive affiliative relationships with a sexual partner. But one of the other species that does is, is this prairie vole, which is a vole species in North America. And what a number of workers in the United States showed was that this bonding behaviour does seem to be absolutely dependent upon oxytocin release into the brain.

The prairie vole is a lovely little animal. They are very, very sociable that they can spend their time in a bonded pair, cuddling side-by-side. They share the housework washing up and the rest of it, well, they share the care for their young. And this bond is very long lasting and it's forged by the first time of sexual interaction. So when a boy meets girl, though, and they are engaged in sex for the first time, it's a very intense experience. It lasts more or less, 36, 48 hours, pretty well continuous copulation. And this has interesting and persistent effects on the brains of both the males and females. Now, what we did know already was that in sexual behaviour also causes the stimulation of oxytocin release into the into the blood and into the brain so that the workers in the states, Tommilson and others, they showed that the locking this blocks the formation of this bond. So that was the key bit of information tying oxytocin actions in the brain into what you call social or affiliative behaviour. And that caused a huge amount of excitement.

Georgia: It’s a delightful tale of prairie vole romance, to be sure. But things get a bit more murky when we try to extrapolate from vole meets vole to our own human behaviours.

Gareth: And there are also big species differences in where the receptors for oxytocin are, because oxytocin is released in the brain, it acts on receptors in particular parts of the brain. And there are big differences from one species to another where those receptors are located. Even in closely related species - the prairie vole is a monogamous species, but there's a closely related species called the Meadow vole, another one called the Montane vole. Well, they are promiscuous and they differ not in the oxytocin systems, but in where the oxytocin receptors are located.

Georgia: And a lot of the studies that claim to measure oxytocin release in humans, well, to put it politely... Gareth is not impressed

Gareth: Well, there's a lot of wishful thinking there. It's really difficult to measure oxytocin release. And in a lot of these studies, it's just basically assumed that there's oxytocin released without any kind of evidence for it. It's not easy to measure oxytocin release and there haven't really been very many very good studies done, especially in humans since it’s really invasive and not easy to do.

Georgia: Is there a link between oxytocin - suspected or even with evidence - and mood?

Gareth: Well, again, there are a lot of it is probably wishful thinking. There isn't really very much direct evidence in animal studies. We do know that oxytocin in some species, anywhere where it's been studied, then oxytocin does have roles in what you might call alleviating stress or alleviating anxiety.

There is good evidence from animal studies that oxytocin is effective at alleviating anxiety. And indeed, what we do, again, know that if you look at animals that don't produce oxytocin and these are transgenic rats or transgenic mice that lack oxytocin, then one of the things is that they have got what are called defects in social behaviour in mice with their oxytocin. Actually, one of the problems is that they have is that they can't remember knowing another mouse that they failed to lose that kind of social memory or they're not able to form it as well. Um, now, what is it about social memories? What is it about social behaviour? Uh, now, actually, if you're if you meet a stranger and if you're a rat, you meet a stranger and then you're wearing. Right, in order to make a connection with that person, you have to break down an instinctive feeling. So anything that will reduce fear and anxiety will tend to favour social interactions. And so that is possibly why oxytocin and social behaviour and oxytocin bonding and what makes sense of that, if you like, that oxytocin is anti-stress, antianxiety, which makes it easier to form connections with other people.

Georgia: So while we probably can legitimately call oxytocin the cuddle chemical, don't believe everything you read about it. In fact - that’s the problem with most of this happy hormone science - it’s mostly happy hormone hype.

Andrew: I think, you know, just a quick glance on the Internet. If you put in happiness and hormones, you end up with a whole lot of, obviously, commercial websites trying to sell you various sorts of supplements of different sorts. But also it tends to be a focus very much on neurotransmitters, on central nervous system processes.

Georgia: This is Andrew Steptoe, professor of psychology and epidemiology at University College London, where he’s head of the Department of Behavioural Science

Andrew: So the work on hormones really comes from a more rigorous scientific background where the amount of evidence is somewhat limited and it's limited in part by the sorts of things that we can measure. So the main hormone that has really been studied in relation to wellbeing is cortisol. And I suppose that's not a complete surprise because we know that cortisol is related to depression. It's also, of course, a stress hormone increased in times of stress. And so you might expect the reverse to be the case, the kind of reciprocal association that people with greater levels of wellbeing might have, lower cortisol levels.

Yes, we’ve got one final surprise hormone for you, and it’s one we keep returning to...

CORTISOL

Andrew: The evidence is really of two sorts. One is essentially correlational evidence relating cortisol levels with levels of wellbeing, be it happiness or purpose in life or other aspects of wellbeing. And the other type of evidence comes from experimental studies, where we put people under stress, under controlled conditions, and then see whether people who have high levels of wellbeing are more or less responsive than those who do not have high levels of wellbeing.

And over the last 20 years or so, it's emerged from large epidemiological studies, which are studies of very large populations that if you measure positive wellbeing in a large population and then you follow people up over time, those people who are happier or enjoy their lives more or have stronger purpose in life seem to be at lower risk for the development of many health conditions, particularly cardiovascular conditions, and indeed amongst older people have longer survival. And this has been a very obviously interesting and exciting notion. But what this has led to is trying to understand what the mechanisms are. And so cortisol or low level of cortisol could be part of that mechanism linking higher positive well-being with better survival.

Georgia: Do you think that there ever might be a way to sort of pharmaceutically improve your mood by dampening down cortisol responses or some way to hack our minds to make ourselves more cheerful?

Andrew: Well, that's indeed the critical question, because a lot of this work is cross-sectional. And so, you know, cause and effect is very difficult to distinguish. What people have tried to do so far is to try to change wellbeing and then see what happens to cortisol. And there's a certain amount of evidence that if you do, you know, do things which improve well-being, you may reduce cortisol levels during that sort of causal link. The trouble is, we're not actually very good at improving people's well-being, at least not for long time periods. As for the other side of it, if you change the hormone levels, you might be able to improve your mood. I think the evidence is still very slender in that area. It is difficult. And the other thing to remember as far as health and wellbeing is concerned is that hormones don't work in isolation. And in particular, they work very closely with immune processes. And it could be that some of those immune processes are just as important as the hormones. And so looking carefully at that link, I think it is very important.

Georgia:  I mean, if you could have a nasal spray that makes you happy, like I can imagine, that would be quite the popular intervention.

Andrew: Well, and if we knew how to make people happier in general, I wouldn't be spending my time sitting here. I would be on a beach somewhere with millions of pounds.

Georgia: Maybe that’s the secret…

Andrew: think the other thing to think about is whether even if you see these associations, whether a supplement is going to be helpful, because we know that supplements work very differently from the kind of naturally occurring hormones and other substances because of the metabolism is and how they get into the bloodstream may be rather different from what happens in, you know, in under the natural circumstances. And so the impact of supplementing any of these things is going to be not obvious as it has to be tested out. And, you know, the simple model, you know, such and such a hormone is too high or too low. And so we can just supplement it and redress the balance. It just doesn't seem to operate in that kind of way.

So are there any science backed ways to improve our moods?

Cathy: The best things we can do for mood and feelings of happiness are the harder things no one wants to do, which are lifestyle changes. Thinking about how much exercise you take, how much sleep you get, what you’re eating, making sure you drink plenty of water, avoiding things like alcohol and other drugs because that’s not necessarily good for our health. But also thinking about our social behaviour. You know, given the last 18 months or so, the pandemic and the social isolation has been a real challenge, I think, for many people. And we know that social behaviour, we are a social species, humans are social, and that it's part of an important part of probably what does make us happy. And this is why hormones like oxytocin, for example, may play a really important role, because we know that they release and influence our mood from social interactions and social situations. And so I think that's something that's been really difficult. And perhaps people appreciate more how important it is to have, you know, close relationships or interactions with your friends and your family. But even just with, you know, everyday people, I guess, on the street, because it is something that we know is rewarding and does, you know, trigger changes in chemicals like 5-HT, serotonin, dopamine and certainly oxytocin. And so that's not really something we would have necessarily thought of before. Is a lifestyle an important lifestyle activity, having a good social interaction? But I think it's something more than ever. We realise how important it is, you know, potentially as important as having, you know, making sure you're sleeping enough and getting exercise.

Georgia: What have we learned? Well, so-called happiness hormones aren’t always hormones, and they're not always that closely linked to happiness. Our moods are made from a complicated hodge podge of these chemicals, and of course our environment. Drugs can be useful for people with anxiety or depression, but they don't work for everyone - and we don't always know exactly how they work - and they can come with side effects.

So what can you do to hack your hormones for happiness? There’s truth to the boring basics, sleep, nutrition and exercise, but really - if something makes you happy (and not in a dopamine addicted kind of way) then you don't need a scientist to tell you how it works.

And - especially after the last couple of years, a few more cuddles definitely couldn't hurt.

Thanks very much to our guests, Cathy Fernandes, Gareth Leng and Andrew Steptoe

This was a First Create The Media production for the Society for Endocrinology

Kat Arney is the executive producer.

And special thanks to Lynsey Forsyth and Natasha Bishop.