How Cocaine Works in Your Brain

Euphoria, stress & the power to change your genes

Rajeet Singh
Jan 4 · 8 min read
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Photo by Alexander Krivitskiy from Pexels

Cocaine is probably the world’s most popular hard drug. Produced mostly in Colombia and consumed by the rest of the world, especially the US and UK, the cocaine market has an estimated global value of $120billion.

Where does the characteristic euphoric & energetic high come from though? And why can it be so addictive?

Cocaine’s neural mechanism is fascinating and affects the brain more deeply than we first realised.

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1. Euphoria and Confidence — Dopamine

Cocaine’s primary effect is in how it affects the brain’s dopamine supply. Dopamine is a well-known chemical; it’s responsible for pleasure and is released when we do things like eat or have sex.

It’s involved in motivation and reward-based behaviour; when we do something our brains deem good for our survival it rewards us with a hit of dopamine. This is so we associate the behaviour with pleasure, motivating us to do it again.

This particular mechanism takes place in the specifically in the nucleus accumbens (NAc), located in the mesolimbic pathway — the brains reward centre — where the concentration of dopamine receptors is high.

Your brain cells have two distinct ends; one end sends signals and the other receives them. The sending and receiving ends of separate cells face each other but don’t touch. The tiny gap between them is called the synapse, or synpatic gap.

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Neuron and Synapse

Signals are sent between brain cells via chemical messengers called neurotransmitters, like dopamine. Dopamine is released from the sending cell into the synapse and activates receptors in the receiving cell, like a lock in a key. (Have a look here for a more in-depth look at how brain cells work)

Once dopamine activates its receptor a pleasure signal is sent down the receiving cell as a result. The dopamine then pops out of the receptor and flows back into the synapse and up into the sending cell once again — this process is called reuptake.

Cocaine hijacks this system by flooding the synapse with dopamine and then blocking reuptake. The practical effect is a load more dopamine molecules swimming around in your synapses and constantly activating your receptors. This sends far more pleasure signals through your brain cells than normal.

In addition, cocaine also affects the immune system’s glial cells. It does this at a specific receptor which results in an inflammatory response in the brain, further exiciting neurons and releasing even more dopamine.

This is where the pleasure and euphoria part of the cocaine high come from.

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2. Energy and Heart Stress — Norepinephrine

Cocaine also affects your norepinephrine receptors, much like it affects your dopamine receptors, but in less intensity.

Norepinephrine (also called noradrenaline) is a hormone associated with your fight or flight response in your sympathetic nervous system. It increases your heart rate, forces blood to your muscles and kicks up your blood sugar.

The staple energertic, ‘invincible’ high of cocaine comes from the mixture of dopamine and norepinephrine activation in the brain, which is why a user can feel energetic and euphoric at the same time.

However, norepinephrine also has an effect on your veins. As well as increasing your heart-rate, cocaine also narrows your blood vessels. An increased heart-rate coupled with decreased space in your vessels for it to flow causes a sharp rise in blood pressure. Much like the pressure of the water coming out of a hose sharply rises if you increase the water supply and squeeze the pipe.

This places stress on the heart and vascular system, especially in repeated cocaine use.

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3. Stress — The Ventral Tegmental Area

The mesolimbic pathway, the area of the brain where cocaine most affects the dopamine supply, originates in a region called the ventral tegmental area.

Apart from norepinephrine cocaine doesn’t seem to affect any other stress hormones, but the ventral tegmental area seems to be a critical integration centre in the brain.

It relays information about stress, pleasure and other cues to the rest of the brain. Cocaine’s activation of the mesolimbic pathway can also have the effect of pushing stress cues to the rest of the brain, since it originates in a key integration centre.

The possible stress effect of cocaine will mostly be overshadowed by its pleasurable and energetic effects, but can become more apparent with constant and repeated use.

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4. Addiction — Gene Expression

This is probably the most fascinating part of cocaine’s neural effect (at least I think it is). Cocaine has the potential to be horribly addictive, but it could never be adequately explained by just its effect on the brain’s dopamine system.

Recent research has found cocaine has the potential of changing gene expression. That means it can change how your genes react and create cells.

We each have roughly 30,000 genes. These genes exist in every cell in our bodies and define what cells are, how they form and how much work they can handle. Every cell has the capacity to change its level of activity based on the demands we place on it.

For example, say you’re lifting weights. The more you use your muscles the more your muscle cells will adapt to the demands you place on them. The more weights you lift, the more work the cells will be able to deal with and the stronger your muscles get.

They do this via gene expression. Certain genes within each cell deal with the capacity of that cell to output or reflect a certain action, like a dial.

Cocaine can alter the expression of numerous genes within the part of the brain it affects the most; the Nucleus Accumbens (NAc), located in the mesolimbic pathway — the brain’s reward centre.

The most interesting of these is the protein ΔFosB. It’s a pace-setting chemical and a gene transcription factor. This means it’s a chemical which sets gene expression. Cocaine causes the build-up of ΔFosB in cells in the NAc.

Experiments with mice showed that high ΔFosB levels led to a change in their cell’s gene expression, making them far more prone to addictive behaviours. Conversely, the lack of ΔFosB led to the opposite effect.

ΔFosB cranks up the ‘addictive behaviour’ gene in cells. ΔFosB naturally lasts about 6–8 weeks before it breaks down, so repeated and regular use of cocaine builds it up to high levels in cells.

When the cells replicate they do so with the new gene expression, meaning new cells will have the same addictive gene dial cranked all the way up.

This addictive behaviour default originates in the part of the brain responsible for reward and positive association. This causes more addictive patterns in anything the person does, since all reward behaviour flows through the same area of the brain cocaine affects.

Regular cocaine use can actually change your genes and give you more of an addictive personality.

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5. Long Terms Personality Changes — Neural Adaptation

Repeated cocaine use has other potential long term personality changes, other than changing the expression of your genes.

The brain is an amazingly adaptable machine, the name for which is plasticity. It has an idea of what its ideal levels of dopamine should be, so when there’s too much flowing around in the synapses for too long the brain can adapt in response. It can either cut down its dopamine supply or remove dopamine receptors from the receiving cells.

The brain requires a certain level of dopamine activation to maintain mood and proper function. Lack of dopamine or of dopamine receptors are the main factors that can give users physical withdrawal symptoms. There simply isn’t enough dopamine activation to reward positive behaviours and maintain mood.

This is also part of where the comedown of a cocaine hit comes from. When the drug wears off the brain breaks down the dopamine used. This means there’s less of it after a cocaine hit than there was before, and therefore less dopamine activation. Your brain needs to build its supplies back up to return to a normal level of activation. How much cocaine a person uses is directly related to how intense the high is, how much dopamine is hijacked by the drug and consequently how much dopamine is lost afterward.

The other fascinating reason cocaine could cause long-term neural changes is again from its stimulation of ΔFosB creation. In addition to dialling addictive behaviours ΔFosB can also increase nerve cell growth (through a gene called CDK5). Elevated levels can lead to cells in the NAc growing more dendrites; the parts of the brain cell that pick up signals. It’s like having a large TV aerial ; the fact it’s bigger means it can pick more signal.

More dendrites in a cell means they can pick up more signals from other cells and therefore other parts of the brain can have a greater effect on them. Since those cells are in the part of the brain which deal with reward-based behaviour, it can bring about long term changes in how the individual perceives many things like memory, emotion and learning, all related to reward-based behaviour.

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Cocaine is a fascinating, powerful and potentially very dangerous substance. It can cause long-term changes to the brain, make a user’s personality far more addictive and can negatively affect the heart and vascular system. Research continues on this most popular of illicit drugs and we’ll find out more as time goes on.

Obviously, this piece is for information purposes only and does not condone or encourage the use, manufacture of purchase of cocaine or any illicit substances.

YouTube: RajeeTV

Twitter: @rajeet_s

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