Addiction Treatment Blog

In 1954, Olds and Milner discovered that there appeared to be pleasure spots in the brain. Implanting electrodes in certain areas of the brain, through which a rat can give itself an electric current by pressing on a lever, produced in most brain areas nothing of note. In some areas, however, the rats seemed keen on the effects of self-stimulation and, in some cases, if left to their own devices would self-stimulate to the exclusion of all else – even food and drink.

As mentioned, noradrenaline was discovered in the brain in 1954. In 1959, a second catecolamine, dopamine, was identified, which was shown to be deficient in Parkinson’s disease.

The later mapping of dopamine-containing neurones has shown that they too, like noradrenergic neurones, tend to originate in a discrete area, the ventral tegmentum. Some of these neurones run to strictly motor areas of the brain and constitute the nigrostriatal system, and it is loss of nerve calls in this pathway that leads to Parkinson’s disease.

Others run to higher areas of the midbrain and to cortical areas. It appears that these are centrally involved in what is termed incentive learning – the kind of learning that occurs when an animal encounters a biologically important stimulus, such as food or a potential sexual partner.

The ventral tegmental system seems closely associated with the pleasure systems discovered by Olds and Milner. But the picture has become far more complicated. It now seems that far from there being pleasure hot spots in the brain, that there are areas of the brain that respond to familiar signals pleasurably and unfamiliar signals with displeasure. Pleasure seems to be a function more of the familiarity of the message being relayed through the system. Things we are familiar with are pleasant, provided we don’t get too much of them – other things are either unpleasant or are reacted to neutrally at first.

Craving

Why do so many alcohol or opiate users return to their addiction, once they have been dried out? If the terror of withdrawal were such significant factor in producing chronic abuse, it might be expected that once freed from the clutches of the demon substance, anyone would keep well clear of further involvement. What perversity of self-destructive impulse is it that leads to further abuse?

The customary response to this has been distinguish between physical and psychological dependence. It is usually argued that the latter is the state of mind, one which stems from deep-seated psychological difficulties. It is this state of mind that some people see as the real problem with the addictions. While it is relatively easy with modern technologies to take in drug addicts and ‘dry them out’, it is a much more difficult problem to ensure they remain drug-free.

When asked why they return to their habits, the usual response on the part of the sufferers is in terms of cravings. The notion of cravings seems to suggest a depravity or perversity in keeping with the social opprobrium accorded to addicts. It suggests some weakness on their part, that fits in with the idea they have psychological difficulties. Current research suggests this picture is quite wrong.

It seems increasingly that cravings are a very tangible, physical reality, and that the form of dependence of another sort. In favour of this argument is the fact that not all drugs of abuse cause cravings. Cocaine, the amphetamines, nicotine, alcohol and the opiates notably do. But LSD, phencyclidine and the psychedelic drugs generally do not, and there is some question about whether the benzodiazepines do or not.

Behavioural Sensation

In the past decade, experimental work on drug effects on the brain has revealed that continued administration of certain drugs, far from leading to tolerance, appears to produce just the opposite effect, even when the environment is held constant. Indeed in a mirror image of the production of tolerance, the holding of the environment constant in these experiments appears to facilitate the production of increasingly enhanced effects in response to certain drugs.

This phenomenon has been called behavioural sensation (1,2), and certain drugs induce it while others do not. Morphine is capable of inducing both sensitisation and tolerance within one animal, tolerance to some effects such as analgesia, and sensitisation to others, one of which is the fact that continued intake becomes increasingly pleasurable.

Initial experiments suggested that morphine produced behavioural inactivity and was somewhat unpleasant. Animals who were linked to electrodes connected to so-called pleasure spots in the brain, were less likely to self-stimulate themselves when given morphine. This ran contrary to the popular belief that opiates were in some way pleasurable, even though, it should be noted, the experience of many people trying them for the first time is that they are not very pleasant.

Subsequent experiments demonstrated that morphine becomes increasingly pleasant to take. Chronic exposure to morphine gradually brings about increases in activity and self-stimulation, in experimental animals. There is an odd aspect to this, which is that such increases are at their height some 3 hours after morphine administration, in contrast to analgesia, which is at maximum after 1 hour.

In line with analgesia, maximal brain levels of the drug occur 1 hour after administration, and not 3. Furthermore, analgesia and the respiratory depression brought about by morphine can be antagonised by morphine antagonists, such as naloxone, but the pleasurable effects of the drug are not antagonised by naloxone.

Appetites

What is happening? It appears that morphine, alcohol, cocaine and amphetamines feed into the brain systems responsible for the generation of and satisfaction of appetites, of which the ventral tegmental system is a component part.

A moment’s reflection should indicate that the last thing an appetitive system could do with is tolerance to the sight of food, drink or sex for example. Rather just the opposite. In contrast to the effect of environmental cues helping to bring about tolerance because they signal the non-threatening or insignificant nature of what is happening, one might expect environmental cues to take on significance where appetites are concerned. That is, we will become increasingly sensitive to aspects of an environment that indicate the possibility of food or sex or drink. Such cues should lead to increased rather than decreased interest.

This seems to be exactly what happens to all of us where our appetites are concerned. Typically we do not notice the accumulation of environmental prompts pushing us toward the consummation of an appetite, unless we have been removed from the environment artificially for a while. Try dieting, seriously, and you will suddenly become aware of all the prompts to eat in the environment – advertisements in magazines, smell of food cooking, etc..

The effect of pubs and the cultures surrounding both drink and drugs provides a host of small prompts, each of which prime an appetite that has already been created. This can even extend to a drug appetite aroused by the sight of needles.

Once stimulated, appetites, while not imperative, have a way of grabbing attention. It is natural to bend our minds to our appetites when they require satisfaction. As the cues to indulgence build up, we typically come closer and closer to behaving on automatic pilot. We regard alternative cues in the environment less and less. Thus the hacking cough is not registered as we light up another cigarette or the number of meals and amount of food we eat are not realised as we sit down for a little soothing snack, while we worry at the same time about our figure, and the children’s Christmas presents are forgotten until the drink runs out.

Shakespeare has put this well in Sonnet 129, where lust is concerned, but exactly the same dynamics apply to food, drink, chocolate, opiates, alcohol, amphetamines and cigarettes:

The expense of spirit in a waste of shame
Is lust in action; and till action, lust
Is perjured, murderous, bloody, full of blame,
Savage, extreme, rude, cruel, not to trust;
Enjoy’d no sooner but despised straight;
Past reason hunted; and no sooner had,
Than past reason hated, as a swallowed bait,
On purpose laid to make the maker mad:
Mad in pursuit and in possession so;
Had, having, and in quest to have, extreme;
A bliss in proof, and proved, a very woe;
Before, a joy proposed; behind, a dream.
All this the world well knows; yet none knows well
To shun the heaven that leads men to this hell.

The establishment of such appetites can be blocked. For example, giving morphine accompanied by dopamine blocking drugs (neuroleptics) or naloxone does block the development of behavioural sensitisation. But once appetites have been established, it is not clear that even such artificial appetites can be completely extirpated. Neither opiate antagonists nor neuroleptic appear to abolish cravings for opiates once they have become established.

It does not make sense that appetites could be abolished – controlled, perhaps, but not abolished. It is possible to manage one’s appetite. For example, the amount of food habitually taken bears some relation to the amount of food felt to be needed. Thus eating a lot creates a big appetite. Decreasing one’s intake can lead to reduced cravings. Similarly sexual appetites are to some extent set by the frequency or indulgence. The notion that some of us are born with greater sex drives than others has little solid evidence in its favour. But, even in the case of total abstinence, we would not expect our sexual appetite to vanish entirely.

However, while appetites once established may not be readily abolished, the notion of craving should not be taken to imply that something has been created that is insatiable and beyond human resources to combat. For example, opiate induced craving, while a real phenomenon, does not appear uncontrollable. Rather as the experience of American GIs returning home from Vietnam suggests, the vast majority of regularly indulging individuals can put aside the habit. This is particularly likely to be the case when they are removed from social situations conducive to it. Once removed from the environmental cues which prompt cravings, only a minority of individuals have overwhelming difficulties.

Current therapeutic strategies are increasingly leaning toward the management of cravings on the model of managing appetites for food, when these are disordered as in bulimia or anorexia nervosa. The issue is often one of helping the individual set a reasonable management strategy rather than having them insist on complete self-control. For example, subjects with bulimia will often plan to eat only one meal a day. This leaves them liable to overcome by hunger pangs on some other occasion, when they guiltily take a rushed snack. Eating it too quickly, they find it unsatisfying and they take some more and end up eating a mountain of food and feeling even more guilty afterwards. Management aims at recognising when an appetite has been stimulated and how to handle it at that point, in a manner that allows the individual to bring into play the usual controls we all have where appetites are concerned, but regarding which we do not normally need to be aware.

The Pharmacological Management of Appetites

A stand by of alcohol treatment programmes for many years has been the use of disulfiram (Antabuse). This operates on behavioural principle and aims at abolishing an appetite or helping with its control. Alcohol in the body breaks down to an aldehyde compound and then an acid. Disulfiram blocks the conversion of the aldehyde to acid, which leads to an increase in the amount of the aldehyde in the blood stream. The consequences are that after a beer or two, subjects taking disulfiram may feel extremely nauseated and/or have a severe headache, and this most unpleasant experience is supposed to deter them from taking any more alcohol. In practice, if individuals want to drink they simply do not take their disulfiram that morning.

A similar approach has been taken with opiate users. It is common in a number of centres for opiate users who have been detoxified to be put on maintenance naltrexone. This is supposed to block the pleasure which they would get from their drugs. There is some debate about how well it does this. There is a further problem in that naltrexone can cause dysphoria in its own right, which in the case of an opiate user might make them liable to seek out a little soothing relief. In all cases the use of naltrexone should be delayed until the user has been opiate-free for at least 5 days, because of the risk of precipitating withdrawal. The initial dose of naltrexone is 10 mg per day, increasing to 150 mg over 2 weeks. The effects of naltrexone last up to 3 days and therefore dosing need only be every 3 days.

But there is another use for naltrexone that has emerged recently, which stems from the likely role of brain opioid systems in the genesis of appetites. A number of trials have now indicated that the use of naltrexone by alcohol dependent individuals reduces their risk of relapse probably by reducing craving (3). This has led to license for its use for this purpose in the US, although not yet in the UK.

References

1. Hand TH, Franklin KB: Associative factors in the effects of morphine on self-stimulation. Psychopharmacol 1986, 88:472-479
2. Jaffe JH: Addictions: what does biology have to tell? Int Rev Psychiatry 1989, 1:51-62.
3. Volpicelli JR, Alterman AJ, Hayashida M et al: Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 1992, 49:876-880.

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