Nov. 6, 2007 According to the Trimbos Institute, anyone who sniffs cocaine once has a 15 to 20% likelihood of becoming addicted to this hard drug. Why does the recreational user only try it once whereas another person becomes physically and mentally dependent on the drug? Behavioural Pharmacologist Inge de Jong, attached to the LUMC (Leiden University Medical Center) and the Faculty of Mathematics and Natural Sciences, sought an explanation in the effect of stress hormones.
The nervous smoker
‘Experience has shown that stress can lead to addiction,’ de Jong says. ‘Take the example of a smoker: he will light a cigarette immediately when he gets nervous. We still don’t understand the physical mechanisms by which stress contributes to the development of an addiction. Certainly for such a highly addictive substance as cocaine, which has adverse effects on health, on the ability to function in society and on criminal behaviour, it is especially important to gain a better understanding of how these mechanisms work. This may enable us to cure people of their addiction,or even better, to intervene preventively.’
How does a person become addicted to cocaine? The more frequently an individual uses the drug, the greater the desire for it becomes, and certain physical reactions also become increasingly stronger. This effect is called sensitisation. De Jong examined how sensitisation is affected by two hormones which are produced by the adrenal glands: adrenaline and corticosterone. She also investigated whether this relation is dependent on the individual’s genetic code. ‘Certain people are by nature more sensitive than others to developing an addiction,’ according to De Jong.
In stressful situations, when there is an external threat, for example, adrenaline and corticosterone are excreted to allow the body to take action. They cause the heart to beat faster and increase the blood supply to the muscles. Normally this response has a functional purpose, such as being able to escape quickly from a threatening situation. In a person using cocaine, however, these stress hormones might have the undesirable effect of encouraging addiction, as they affect those areas of the brain that cause the body to crave more of the drug.
De Jong tested this reaction on mice. She used two different breeds of mice which differed in their sensitivity to drugs and stress. Sensitisation appeared to occur in both breeds: with repeated cocaine injections, the mice became increasingly physically active. De Jong investigated the contribution of stress hormones to the sensitisation process by surgically removing the mice’s adr enal glands. She then administered corticosterone and/or adrenaline to the animals.This enabled her to study both the individual effects of these hormones as well as their combined effects.
What results were gained from this research? Removing the adrenal gland, and thereby halting the production of corticosterone and adrenalin, had the effect of reducing cocaine sensitisation in one breed of mice. It was only when the two hormones were both administered artificially that sensitisation reoccurred. ‘Stress hormones can therefore contribute to cocaine addiction,’ De Jong concludes. ’But this only applies to individuals with a particular genetic code.’
The PhD researcher suspects that this conclusion also applies to a greater or lesser extent to other hard drugs. However, she recognises that prudence is called for in transferring her conclusions on mice studies to humans. ‘For ethical reasons it is difficult to conduct such experiments on people,’ she says. Nevertheless, earlier research has indicated that stress hormones may also play a role in cocaine addiction in human beings. People with a post-traumatic stress disorder are thus more likely to suffer from an addiction. Moreover, administering corticosterone to addicts increases their desire for the drug.
De Jong sees in these results some opportunities for the treatment of addicts. ‘If we can block the unwanted effects of the stress hormone medicinally, we may possibly be able to reduce the need for cocaine. Not everyone is genetically sensitive to addiction, but stress is certainly a risk factor to which we must pay more attention in people who are in danger of becoming addicted to cocaine.’
De Jong defended her thesis on 17 October.
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