In recent decades, there has been a vast improvement in our understanding of drug action in the brain. This includes cocaine, which is the second most frequently used illegal drug worldwide, after cannabis. However, despite knowing the basic neurobiology of cocaine action in the brain, scientists are still working hard to understand how this translates to addiction and what the determinants of cocaine-seeking behaviour are.

Here’s a quick intro. Neurotransmitters, as most of you may know, are substances that neurons use to communicate with each other. There’s an important category of neurotransmitters called monoamines, which include dopamine, noradrenaline and serotonin. When they are released, they excite or inhibit other neurons but they are ultimately taken up back into neurons via monoamine transporters, which terminate their action. Cocaine blocks these transporters, particularly the dopamine transporter, causing dopamine to flood the brain and elicit agitation and euphoria. Drugs are initially taken because the increase in dopamine causes feelings of pleasure. Eventually, the reward circuitry adapts to the increase in dopamine and develops tolerance, meaning that you need more dopamine each time to experience the same amount of pleasure. This eventually leads to addiction, characterised by chronic compulsivity.

The main reward pathways involve the striatum and the amygdala, structures found buried deep in the hemispheres. In a study using mice, it was shown that brain activity during the initial goal-directed phase of cocaine seeking was different to that of cocaine seeking that has become habitual and chronic. Goal-directed cocaine seeking is associated with activity in the basolateral amygdala and the core of the nucleus accumbens, in the form of Pavlovian conditioning that involves reinforcement of the behaviour by drug-related stimuli.

Wikler’s 1948 theory of relapse characterises addiction as the compulsive avoidance of severe physical withdrawal symptoms. Cocaine, however, does not cause prominent physical dependence. Instead, the drug is more involved with psychological withdrawal symptoms, mainly feelings of craving. However, statistics have shown that six out of ten cocaine addicts relapsed for reasons other than craving the drug.

What could be causing it then? It was previously thought that relapse is caused by reduced control of the frontal lobes, namely the prefrontal cortex. However, a new study led by Dr Belin from the University of Cambridge has discovered a new component of the reward pathway that bypasses the prefrontal cortex, connecting the basolateral amygdala (associated with emotional experience) with the dorsolateral striatum (associated with habitual behaviour). This means that feelings of craving are essentially unconscious – the drug addict may not be aware of their desire to take the drug. This seems like a vicious cycle: the more cocaine you take, the more you crave it, the more you change your behaviour in order to satisfy this craving, until it becomes second nature. Not only can you not control it: you may not even realise it!

Dr Belin showed through a second study that N-acetylcysteine (NAC), a drug used to treat paracetamol overdose, might help addicts overcome their addiction by decreasing activity in the reward pathway described above – but only if they are determined to quit. This study is still in the clinical stages, so I wouldn’t depend on endorsing that treatment just yet.

What both of these studies hint is that prolonged cocaine intake causes cocaine-seeking behaviour to shift from goal-directed (under voluntary control) to compulsive (involuntary). The fact that addiction is due to lack of control is nothing new, but the prospect that our brains can be controlled by drugs even under the level of consciousness is frightening for those who want to quit.

However, research in the area is far from over. Hopefully, in the near future, scientific knowledge will allow us to invent both remedies and, more important, means to prevent addiction from occurring in the first place.