Sensitisation

Sensitisation is the process of becoming more sensitive to a drug from repeatedly taking it. This can be a confusing concept, as it’s generally understood that we become less sensitive to the effects of drugs over time and build a tolerance.

It’s true that tolerance for the intoxicating effects of drugs, such as euphoria, increases from repeated exposure. So why do we talk of becoming more sensitive to drugs?

A more accurate term for this process would be incentive sensitisation. You may still need more of the drug to achieve intoxication, but drugs affect you in many ways – and you can become more sensitive to other aspects of the drug, not just their intoxicating properties. Sensitisation and tolerance can occur simultaneously – they are separate processes.

The incentive sensitisation model of addiction

In the incentive sensitisation model of addiction, you become more sensitive to wanting drugs rather than more sensitive to the intoxicating properties of the drug. 

To understand incentive sensitisation and addiction, we need to break down the difference between ‘wanting’ and ‘liking’ and how that looks in the brain.

1. Wanting is a process that drives drug-seeking behaviour, and in psychology this is also known as incentive salience. Incentive salience is the motivation or drive to get a reward – it is not the same as liking. Wanting/incentive salience is driven by the mesolimbic dopamine system. Dopamine is highly associated with goal-seeking, reward and desire.
2. Liking does not rely as heavily on dopamine and is more associated with areas like the brain’s nucleus accumbens – pleasure centres. Understanding that wanting and liking are distinct and affect different brain areas helps us understand a critical element of incentive sensitisation – we can sometimes want things we do not like. Incentive sensitisation theories that circuits in our brain associated with wanting become more sensitive with repeated exposure to a drug, even if areas associated with liking don’t.

How the brain becomes sensitised to wanting

This sensitisation happens in a few ways within the brain as addiction progresses.

Dopamine 

The brain releases dopamine in response to a drug. Over time, as sensitisation occurs, this release becomes exaggerated – the brain releases more dopamine in response to taking a drug. This results in an increase in incentive salience/wanting – you want the drug even more than when you first started taking it.

Structural changes in the brain

Neuroplasticity is the process of the brain changing structurally over time in response to our behaviours and environment. When the brain undergoes incentive sensitisation, there’s an increase in the number and size of dendritic neurons in certain parts of the brain – as there are more of them, they become more sensitive to drug-related stimuli. 

This process isn’t limited to drug addiction either – these same changes can happen from behavioural addictions such as gambling or social media.

These are the main drivers of incentive sensitisation. Other areas of the brain and neurotransmitters are also affected, but the biggest factors are changes in dopamine release and structural brain changes.

Sensitisation and addiction

After the brain has adapted to repeated administrations of the drug and incentive sensitisation has occurred, this manifests in different ways.

Cravings

This process hasn’t just sensitised your brain to drugs – it’s sensitised it to behaviours and situations associated with the drug as well.

This means they aren’t just more sensitive to the drug itself but to cues around the drug, such as paraphernalia, time, place and situation. This can go some way to explaining cue-related drug cravings that persist long after quitting the drug – these cues have taken on an outsized meaning because of these structural changes.

This process has a lot in common with classical conditioning. Ivan Pavlov kickstarted the field of classical conditioning in his experiments with dogs. He noticed that dogs naturally salivated when presented with food. Over time, he rang a bell when presenting the dogs with food, and the dogs learned to associate the bell with food. Finally, he removed the food from the experiment and rang the bell – the dogs salivated. The dogs had learned to associate the bell with the food when, previously, these two things had been unrelated.

While there’s more to incentive sensitisation than this, and Pavlov was not aware of the neurobiological mechanisms driving the dog’s conditioning, it gives us an insight into how we can start associating one thing with another. Pavlov’s dogs could unlearn the association between the bell and the food by being presented with the bell but not the food repeatedly – but it took time to unlearn this association. Additionally, his research suggested that this association could become dormant but never went away entirely. This has implications for cravings during recovery and for the long-term risk of relapse.

Persistence of sensitisation

Tolerance and withdrawal diminish over time, but incentive sensitisation in the brain is much more long-lasting, and some theorise that it may be permanent.

This does not mean addiction is permanent, and people in addiction cannot recover. It means some neural pathways and areas of the brain may retain a heightened sensitivity to drugs and their cues long-term, meaning addiction needs to be carefully managed, and recovery needs to be treated seriously.

Liking versus wanting

While the brain’s dopamine system is becoming more sensitive to drugs in some ways, it’s becoming less sensitive in others. This difference explains how we can want something more while liking it less – and is one of the crueller aspects of how addiction manifests in the brain.

Dopamine release increases in response to drugs as we become more sensitised – and the brain compensates for that. The brain tends to move towards homeostasis and needs a way to counterbalance all the extra dopamine that repeated drug use is releasing in the brain. It does this through downregulation, which happens in the neurons that feel the effects of dopamine release – specifically the D2 dopamine receptors.

D2 dopamine receptors are associated with the pleasurable effects of a drug – we feel good when these receptors receive dopamine. However, if dopamine is artificially increased in the brain over a long period, the brain starts to shut some of these receptors off to compensate for the increased dopamine.

This does several things – it makes the drug less pleasurable, meaning more of the drug needs to be taken to attain a high, and you like the drug less. It also means that small pleasures can no longer compete with drugs as the brain is far less sensitive to dopamine release. 

This process explains the anhedonia and flatness many people experience in recovery. It isn’t permanent, and your D2 dopamine receptors can become sensitised again, meaning you will regain the ability to feel pleasure in smaller things. However, this takes time. The dual challenges of having a brain sensitised to wanting a drug and the cues around it while simultaneously struggling to experience pleasure from everyday experiences is a significant challenge and increases the risk of relapse – only time and refraining from taking addictive drugs can allow the brain to heal and recover.