Mechanisms of addiction
Drug abuse is an increasing problem in our affluent societies and carries great social and economic costs through its impacts on crime and health. Official policy in the Western world for the past 50 years has been to treat addicts as criminals and to punish them, but this has manifestly failed to prevent the increase in drug abuse. Nor have campaigns to educate people about the dangers of drugs, tobacco, and alcohol had anything other than relatively minor effects. From the neuroscientist's point of view addiction is increasingly seen as an organic disorder of brain function; if this could be better understood we might be able to offer more effective treatments to addicts.
The definition of addiction has changed in recent years. The term was previously applied only to such ‘hard’ drugs as heroin, where there are obvious signs of tolerance and physical dependence in regular users, and a painful or even life-threatening physical withdrawal syndrome when drug use is stopped. Psychiatrists now use the term ‘substance dependence’ to include both psychological dependence (where there may be no obvious withdrawal syndrome or tolerance) and physical dependence. The cigarette smoker who cannot stop smoking or the cannabis smoker whose drug habit has come to dominate their life is no less addicted than the chronic heroin user, even though they may suffer only mild withdrawal signs when drug use is stopped.
Great progress has been made in understanding the mechanisms by which the various classes of addictive substances act in the brain. These include the ‘psychostimulants’ — a large group of drugs encompassing cocaine and various amphetamines. These drugs all act in the brain to stimulate receptors that recognize the chemical messenger substance dopamine. Cocaine works by blocking the inactivation of dopamine after its release from nerve terminals in the brain — a process that involves recapture of the released chemical into the nerve endings. Blocking this process makes more dopamine available to stimulate brain receptors. The amphetamines work by displacing dopamine from nerve terminals. The ‘rave dance’ drug, ecstasy, is an amphetamine derivative that combines psychostimulant (dopamine) properties with a mild hallucinogenic effect — thought to be due to stimulation of receptors for another brain chemical messenger, serotonin. The opiates (for example heroin), cannabis, and nicotine all act on specific receptors that are present in the brain and which recognize these different drugs. When the drug binds to the receptor it triggers activity in nerve cells. One might wonder why the brain should contain such receptors, since the drugs themselves are plant products that do not exist naturally in the brain. The answer is that in each case there are naturally-occurring brain chemicals which activate these receptors, and the drug molecules hijack these normal brain mechanisms. Precisely how alcohol works remains unclear, but it is increasingly thought to act by modifying the responsiveness of the brain to the principal ‘on’ and ‘off’ chemical signals, glutamic acid and GABA — thus lowering neuronal excitability.
Knowing how these drugs act, however, does not explain why they are addictive. Furthermore, there seem to be a bewildering number of different brain mechanisms activated by the different classes of drugs. Consequently, great excitement has been generated in recent years by the first glimmers of some common themes of understanding in this area. One important series of research findings points to a common brain mechanism that is triggered by all known drugs of addiction — namely, the activation of dopamine mechanisms in a region of the forebrain known as the nucleus accumbens. This is a small dopamine-rich brain region underlying the larger dopamine-rich movement control centres, the caudate nucleus and putamen. The nucleus accumbens is part of the limbic forebrain, a brain region known to be important in emotional behaviour and in pain and pleasure. By direct measurements of dopamine release from animal brains, using tiny probes inserted into the nucleus accumbens, it has been found that cocaine, amphetamines, alcohol, nicotine, and cannabis all share the ability to cause increased levels of dopamine. When low doses of the drugs are used, the nucleus accumbens is the only brain region that shows such increased levels of dopamine. Furthermore, rats in which the dopamine-containing nerve terminals in the nucleus accumbens are selectively destroyed (by means of the selective chemical neurotoxin, 6-hydroxydopamine) no longer self-administer amphetamines or cocaine. Could it be that dopamine release in the nucleus accumbens is the common mechanism underlying the pleasurable actions of these drugs? According to this view the drugs simply subvert a normal brain mechanism in which pleasurable or ‘reinforcing’ stimuli assist the animal in learning to repeat a behaviour. Addiction can be viewed as an ‘aberrant form of learning’ — the drugs recruit brain mechanisms that have a normal place in cognitive and emotional behaviour and cause these to malfunction, so the addict ‘learns’ to continue using the drug.
Historical perspective
There have been remarkable changes in attitudes to psychoactive drugs in Western society over the years. What was considered safe and beneficial in one era often comes to be seen as an evil scourge to a later generation. Nowhere is this more obvious than in the place that opium has played in British history. Imported as an important trade commodity from Turkey and India, opium was widely used in all strata of British society in the eighteenth and nineteenth centuries. The poor sought solace from the miseries of their daily lives, working mothers used opium-containing ‘cordials’ to calm their children while they went out to work, middle-class housewives took laudanum (an alcoholic extract of opium) to calm their nerves, and artists sought inspiration from it. The literary movement in Europe known as the Romantic Revival relied extensively on opium to free the users to flights of fantasy and imagination, and included such figures as Schlegel, Madame de Staël, and Pushkin, in continental Europe, and Coleridge, Wordsworth, Scott, Shelley, Keats, and Byron in Britain. Thomas de Quincey's famous autobiographical Confessions of an Opium Eater (1821), was the first literary account of the powerful addiction that opium can cause.
In mid-nineteenth-century France, cannabis was introduced from Egypt, following the Napoleonic campaign, and became fashionable among many in the literary world who frequented the ‘Club des Hashischins’ in Paris. The work of Alexander Dumas, Gerard de Nerval, and Victor Hugo was much influenced by the drug, and Charles Baudelaire wrote a classic description of the cannabis (hashish) experience in Les Paradis Artificiels published in Paris in 1860. It was not until the latter half of the nineteenth century that restrictions were placed on the use of opium in Britain. Even as late as 1895, the Royal Commission appointed to report on the use of opium in India concluded that the drug had no harmful effects on the local population. A similar conclusion had been reached a year earlier by the Indian Hemp Products Commission, which reviewed the widespread use of cannabis in India.
In much the same way, when cocaine was first discovered a century ago as the active component in coca leaves, many experts extolled its virtues, and it rapidly gained a short-lived medical acceptance for a multitude of uses. Ironically, one of its popular uses was in the treatment of opium addiction! Sigmund Freud experimented with this and other uses of cocaine and took the drug himself for many years. By the turn of the century, however, the party was over; it had become clear that cocaine was a dangerous drug of addiction.
A more recent example of changing attitudes is the way we view tobacco smoking. Cigarette smoking grew rapidly in the Western world in the first part of the twentieth century. In the US by 1945 half of all adult men were smokers — consuming an average of 20 cigarettes per day. Smoking was glamourized by Hollywood movies and even advertised as having medical benefits. Things began to change, though, after the discovery of the link between cigarette smoking and lung cancer, and the growing recognition that nicotine is a drug of addiction. Today cigarette smokers have become pariahs, no longer permitted to indulge their habit in many public places or on aeroplanes, and tobacco companies are seen as ‘evil empires’.
The historical perspective perhaps teaches us that during the late twentieth century we may have moved towards over-emphasizing the damaging effects that psychoactive drug consumption has on society. While the regulation of such dangerous drugs as heroin and cocaine may be necessary to protect citizens from them, the use of the criminal law to prohibit the use of drugs such as cannabis and ecstasy, which are less likely to cause damage, is less rational. It may have to do with our demonization of drug use as almost a modern equivalent of heresy in the Middle Ages — a crime to be punished by penalties that are more severe than the crime itself.
The way forward
Despite the importance of scientific research in this area for improving future treatment strategies, there is lamentably little effort or resource devoted to it at the moment. In thinking of treatments that might help to wean addicts from their drug habit we need to think of a range of different goals aiming to reduce craving for the drug, assist in overcoming the withdrawal signs ‘both psychological and physical’, and help the reformed addict not to relapse. We are not very close to achieving any of these at the moment. The most effective strategy we have currently is to treat addicts with a safer form of the drug itself — the heroin addict with methadone, the cigarette smoker with nicotine patches or gum. We must learn approaches that are both more sophisticated and more effective if we are to make any real impact on the problem.
— Lesley L. Iversen
Bibliography
- Berridge, V. (1999). Opium and the people. Opiate use and drug control policy in nineteenth century and early twentieth century England. Free Association Press, London.
- Musto, D. F. (1999). The American disease. Origins of narcotic control. Oxford University Press, New York.
- Robbins, T. W. and Everitt, B. J. (1999). Drug addiction: bad habits add up. Nature,
398 , 567-70
See also addiction; drugs; membrane receptors; opiates and opioid drugs.
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