The routes and risks of addiction

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In addition to the impact of drug misuse on the social aspects of life, it can lead to significant medical problems. The dangers of drug abuse relate to two main factors; the route of use of the drug and the effects it has in the brain outside of the reinforcement circuit.

For most drugs of abuse the faster the drugs reach their target site in the brain the better they are liked and the more psychologically reinforcing they are. Indeed, the 'pharmaceutical' history of most abused drugs illustrates the progressive refinement of their preparation, in order to accelerate their rate of entry into the brain. A good example is cocaine. The Andean Indians originally used it by chewing coca leaves which produced low levels of cocaine over a period of time. An increase in vigour and a resistance to fatigue is produced, but little pleasure. Over the centuries cocaine has become more refined, first to paste and then to cocaine hydrochloride powder (snow) which when taken nasally produces high levels in the brain within 5 to10 minutes and a clear 'high.' Further refinement to the free base produces a more lipophilic form (crack) that can be smoked, resulting in entry into the brain in seconds. Intravenous drug use also serves the same purpose of getting the drug to the active site very fast.(35>

A similar process of pharmaceutical refinement to accelerate brain entry has taken place with the opiates. Smoking opium is a method of delivering morphine and related substances reasonably quickly but in low amounts. Refining opium into its active constituents (e.g. morphine) means that higher doses are more easily ingested. However, morphine crosses the blood-brain barrier relatively slowly and has therefore been largely supplanted by opiates such as heroin that cross more rapidly. Heroin is a diacetylated synthetic derivative of morphine that is more lipophilic, meaning that it is able to enter the brain more rapidly and give a better rush. Interestingly, the active form of heroin is morphine; heroin has to be deacetylated before it can act, which proves that pharmacokinetic differences are the critical variable with opiate preference. Similarly, codeine is also inactive until metabolized to morphine, but because this happens very slowly codeine has less abuse potential than morphine.

The benzodiazepines were abused relatively rarely until the advent of gel-filled capsules of temazepam. These provided experienced intravenous opiate users with a convenient source of a concentrated drug which they began to experiment with in the late 1980s. In an attempt to stop this, the drug was reformulated in wax. Unphased by this change, the users started heating up the caplets until they melted and then injecting the hot solution into their veins (hot lining). At body temperature the wax solidified and tended to block the veins and arteries (with missed injections) into which it was administered. Severe ischaemia leading to gangrene and the loss of the limb sometimes resulted. Since there are no therapeutic advantages of temazepam over other benzodiazepines that are much less abusable, this drug has recently been put under a higher degree of control in order to deter its prescription.

As well as affecting the relative reinforcing actions of abused drugs, the rate of brain entry also contributes to risk. A very rapid drug entry makes dose adjustments difficult or impossible and so predisposes to overdose. This is most obvious for intravenous use of opiates where respiratory depression is the main cause of death, but is less common with smoked opiates as intake can more easily be titrated to the desired effect.

The route of use also affects risk, most notably with the risk of infection from intravenous use, especially when needles are not cleaned or are shared. The majority of current intravenous users are hepatitis C positive and we can therefore expect cirrhosis to become a major cause of their death in the next decade or so. This also raises ethical and economic issues; interferon treatment significantly reduces the progression of the disease but is costly and its routine use in addicts would be massively expensive and likely to cause public disquiet. The other main infections are hepatitis B and AIDS. The frightening rise of AIDS in drug abusers, where it occurred faster than in any other group, was the main impetus to the harm-reduction approach becoming the treatment style of the 1990s. Needle-exchange programmes and increased methadone availability were both proven to reduce the spread of AIDS and have become the cornerstone of treatment in many countries.

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