My chemical romance

Ginny Smith picks out six chemicals from her new book Overloaded: How Every Aspect of your Life is Influenced by your Brain Chemicals (Bloomsbury Sigma).

18 March 2021

For me, one of the biggest appeals of the fields of psychology and neuroscience is their ability to answer what is, I think, the biggest question in science: why do we behave the way we do? It seems to me that the answer lies not in the wiring of our brains, but in the chemicals that bathe them. Because while the connections between neurons can and do change, this process is slow. This means it can’t be responsible for the millisecond-by-millisecond changes we all experience: the split-second decisions, fluctuations in emotion and the temptations we encounter. Instead, these are all controlled by our brain chemistry. And, as it is our brain that makes us who we are, that means that we are controlled by this turbulent sea of neurotransmitters.

There are, of course, a huge number of chemicals that affect our brains and behaviour, but in this article I have picked six of my favourites, to give you a taste of their vital roles, and the complexity of the systems that use them.

1. Glutamate
It may not be the flashiest neurotransmitter, but glutamate is the workhorse of the brain. The most common neurotransmitter in the human brain, when glutamate is released by one neuron it travels across the gap (or synapse) and makes the next neuron more excitable. If enough is detected, the second neuron will fire, sending the message on its journey.

Glutamate is vital for learning. Repeatedly activating the same pairs of neurons, by revising a fact or practicing a skill, causes the neurons to change. The first neuron begins to release more glutamate in response to each signal, while the second undergoes changes which free up more receptors. Both changes improve the chances of the second neuron receiving the signal and continuing to pass it on each time the first neuron fires. They also increase the speed of the transmission. This is why once you have learnt something thoroughly, it is easier to recall it, and it feels like it takes less effort. It really is easier for your brain to activate these pathways, thanks to the power of glutamate.

Glutamate isn’t all sweetness and light though. While it is vital for our brain to function, too much of the chemical can be toxic to the brain, so it is vital it is kept in balance. Sadly, boosting glutamate levels isn’t going to help you remember where you left your keys!

Glutamate’s counterpart is Gamma Aminobutyric Acid, better known as GABA. This chemical has the opposite effect to glutamate; when it binds to receptors, it makes it harder for the neuron to send its signal. This makes GABA an inhibitory neurotransmitter. Neurons that use GABA, then, have a calming effect on the brain, reducing the activity of other neurons. This means they are important for sleep (GABA levels in the cortex are high during deep, slow wave sleep), and for counteracting stress.

GABA may also play a role in anxiety and depression. If the balance between glutamate and GABA is off, the brain can be overly excitable, leaving us feeling anxious. Some drugs which are being trialled for treatment-resistant depression, including ketamine and antiepileptic drugs, raise the levels of this chemical, which may, at least partially, explain their benefits.

In healthy people, yoga has been found to increase levels of GABA in the thalamus, and this correlates with reductions in stress and improvements in mood – something we could probably all do with at the moment!

3. Acetylcholine
Our brain has a huge job to do. Two of its most important responsibilities are taking in information from the world around us, and processing memories. But how does it know which to focus on at any point in time? This is where the chemical acetylcholine comes in.

When levels of this chemical are high, you focus on the external world, entering the perfect state to learn new things. After a while, however, acetylcholine levels drop, and your attention starts to drift – you might begin daydreaming, or thinking about what to have for dinner. When you are resting, acetylcholine levels in the hippocampus fall and internal circuits become dominant. This allows memories formed during focused wakefulness to be stored. The same happens when you are in deep sleep.

The right amounts of acetylcholine, at the right times, then, are vital to both create memories, and store them for the long term. This explains why drugs that block acetylcholine receptors, tricking the brain into thinking levels are low, can cause severe amnesia. People become unable to learn, their brains stuck in internal mode. These drugs can even cause hallucinations, possibly as a dramatic shift to focus on internal perceptions causes people to start ‘experiencing’ their memories, believing them to be real.

4. Serotonin
While it is undoubtedly one of the most important chemicals in the human brain, I have a love-hate relationship with serotonin, because of just how complicated its effects can be! When I started the book, I knew it would be important in my mood chapter, and that it would probably pop up in a couple of others. It turned out to be featured in 7 of the 8 topics I cover. And in each, it has a different effect.

Partly, this is because there are at least 14 different serotonin receptors. So neurons respond differently depending on which of these receptors sits on its surface. This means not only can serotonin have different functions in different brain areas, it can even have different effects within the same area.

Despite this, I have a soft spot for the chemical. Having the right balance in each brain area is vital for our brains to work optimally. It has a role in preventing us falling asleep during the day, helping us to use emotions to make decisions, and is linked to the obsessive feelings of early love. It can also ramp up or down pain signals, depending on which receptors are involved.

Then, of course, there are the links with mood and mood disorders. While the details of these are far from clear, there are lots of ways it might be involved – from helping us collect more positive information from our environment to acting as a growth factor, encouraging the birth and growth of new neurons in parts of the brain. Dysregulation in serotonin systems has also been linked to eating disorders, including anorexia, bulimia and binge eating.

5. Caffeine (adenosine)
It may not be a brain chemical, but I couldn’t leave caffeine off this list because its effects on the brain chemical adenosine are why so many of us love it. During the day, adenosine builds up as a by-product of our cells’ metabolism. While we sleep, it is cleared away. So adenosine tracks how long we have been awake, and when we have had enough sleep.

When adenosine levels are low (e.g. after a good night’s sleep), acetylcholine is released in the basal forebrain. This guides our attention towards external stimuli, making us feel awake and alert. When adenosine builds up, it prevents the release of acetylcholine, so we feel sleepy. Caffeine blocks the receptors normally triggered by adenosine, so our brains think the concentration is lower than it actually is. This means more acetylcholine is released making us feel more alert.

Unfortunately, we can develop tolerance to caffeine in just a couple of days. Once this has happened, you will feel more tired and sluggish before you have your coffee than if you had never drunk the stuff. All that first cup does is bring you back up to your natural baseline – although knowing this doesn’t stop me reaching for a cup every morning!

6. Oxytocin
I couldn’t write an article about the chemicals I love without mentioning the love chemical; oxytocin. First discovered to induce labour in pregnant animals and milk production after birth, scientists later found that oxytocin also helps animals bond with their offspring. We now know that the same is true in humans – parents with higher levels of the hormone have stronger bonds with their infants, and giving a parent oxytocin can boost activity in parts of their brain involved in empathy and reward.

But it seems evolution has, in some animals, hijacked this system, and tweaked it to create pair bonds between adults. Evidence comes from prairie voles, one of few monogamous mammals. Unlike their promiscuous cousins the montane voles, prairie voles have receptors for oxytocin and a closely related molecule called vasopressin in the reward circuits of their brain. When they have sex, oxytocin is released, triggering these areas, so they learn to associate their partner with the rewarding effects of sex. That drives them to spend more time together. Block these hormones, and you lose the bonding effect. Humans too have receptors for oxytocin and vasopressin in a range of brain areas that have been linked to love, like the reward system and the limbic system. And oxytocin is released when you feel close to someone – either physically or emotionally, so it seems likely these hormones are vital for bonding in humans too.

So there you have it – my ‘greatest hits’ of brain chemistry. Of course, in a short article like this I can barely touch on the myriad of effects each chemical can have, and there isn’t room to go into the fascinating stories of the scientists behind the chemicals – from the fighter pilot who revolutionised our understanding of sleep to the scientist who disobeyed her boss and discovered opioid receptors in the brain. But I hope you can begin to see the important role these tiny molecules have on all aspects of our life, and the incredible intricacy and complexity of the brain networks that use each one.

- Find more about the book via Ginny's website.