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Looking at the brain to understand drug addiction

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An increasing complexity seems to characterize the scenario of the European drug problem. The picture that emerges from the EU drugs agency (EMCDDA) 2014 report, published last May, highlights a stable general situation, in which new problems and threats appear. Drug users seem to represent a complex continuum from rare experimental use and habitual, compulsive use: a pattern that differs from the old dichotomy between a small group of “hard” drug addicts and a larger group of recreational users. The associated risks can be thus difficult to estimate and predict, often depending on a number of different factors.

According to the report, over 80 million of European citizens have used an illicit drug during their life, almost a quarter of the entire adult European population. New drugs, new consuming behavior: in order to face the problem, different approaches have to be integrated, from social intervention to clinical services to basic brain research.

Which are the contributions that neuroscience research can have in the field of addiction treatment? 

“A first, fundamental change brought about by neuroscience studies is a switch in the perception and conceptualization of addiction,” explains George F. Koob, Director of the National Institute on Alcohol Abuse and Alcoholism of NIH, in Washington DC. “The role of brain in addiction is now widely acknowledged, and it is becoming more and more accepted to trait drug and alcohol addiction as a brain disease”.

George F. Koob is one of the three researchers who received the 2014 Neuronal Plasticity Prize, conferred by Foundation IPSEN during the FENS forum of neuroscience. Together with Koob, two other laureates shared the prize: Barry J. Everitt and Michel Le Moal. “Removing the social stigma from addiction is a first step in trying to address the problem,” adds Barry J. Everitt, professor and director of research at the University of Cambridge. “Suffering from drug or alcohol addiction is still perceived as something to hide. For example, just think about Alcoholics Anonymous: we would not have Diabetics Anonymous or Heart patients Anonymous”. According to the three scientists, a superficial approach to the problem still considers addiction as a bad attitude, not very different from a wrong habit. Taking drugs, or drinking alcohol, is often depicted as something that an addict can avoid. “If we read tabloid press, we can see titles like «You can just say no»,” comments Everitt, “but maybe it is not true, maybe you cannot avoid it, you cannot just say no”.

“The study of the brain and its functioning can lead to a change in the social and clinical attitude towards addiction, as other diseases,” observes Koob. “Before the introduction of antidepressants and thus the understanding that neurons’ behavior is related to the mental and mood state, depression was mainly considered as a problem of motivation. Now we consider it a disease, and we treat it with medicines and therapy. A similar change can happen with addiction”.

Despite the importance of a change in perception with respect to addiction, this is not the only contribution of brain research in this field. Understanding how neurons react to drugs, which mechanisms lead to compulsive use of substances and how individual differences can affect the way in which we interact with drugs are only some of the examples that can stimulate the development of novel treatments in the clinic. In the Department of Psychology at the University of Cambridge, the research group led by professor Everitt studies the neuropsychology of drug addiction, and the relationship between memory and compulsive behaviors. The results of their research could help developing new treatments to prevent relapse and promote abstinence in drug addicts.

“We investigate the role of one type of memory mechanism on addictive behavior,” explains Everitt. “We can imagine how hard it is for an alcoholic to refrain from drinking when he or she enters a bar. There are some stimuli that become associated with the effects of drugs or alcohol: they could be objects, places, even people. These cues can induce craving and drug seeking behavior. So we asked: what if we could reduce or eliminate their ability to influence relapse?”

There are two approaches that scientists can use in order to manipulate the effect of memories on addictive behavior. The first one is the pharmaceutical intervention: some molecules can affect the mechanism involved in the influences of drug-associated cues. However, according to Everitt, it seems that the pharmaceutical industry is not interested in developing a commercial drug with this characteristics. “So we tried a different approach: can we modify the representations of drug-associated cues held in memory?”

By following a specific procedure that involves the use of simple beta-blockers, it is possible to make a memory unstable: the drug-associated memories can be disrupted when they are in such unstable states, preventing the subsequent drug seeking behaviors. The procedure, which has been tested in animals, is now going to involve patients in a community of alcoholics in Cambridge. The idea, explains Everitt, is to include the practice in clinical treatment, for example within a cognitive therapy.

Understanding the reasons that transform a drug user into a drug addict could be of crucial importance to develop clinical treatment for addictive behaviors. Not everyone react at the same way to drug use. “Some addicts go on for months or years using heroin or cocaine only on weekends before becoming daily addicted users; others report that they had such an intense positive response that they became addicted from the first time,” explains Michel Le Moal, professor of neuroscience at the University of Bordeaux.

“For many years, individual differences have been an annoyance rather than a challenge for experimenters: they wanted to study the average behavior. Now we understand that looking at differences among individuals may be the only approach to study some pathologies”.

If we can comprehend why some people are more resilient and others are more vulnerable to addiction, we could find specific treatments or actions to cure or even prevent compulsive behaviors related to drugs or alcohol.  “Addiction is often related to anxiety: drug or alcohol becomes a kind of self-medication for some individuals who are more vulnerable to stress. If we can treat anxiety, we might be able to prevent the development of addictive behaviors in some people. Impulsivity control, another trait related to addiction, can be helped with mindfulness treatment”.

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