THE GENETICS OF HEROIN ABUSE

What are the implications of new scientific findings for effective drugs
treatment?

There is a significant, but not exclusive, genetic influence on the
development of opiate abuse and dependence.

The exact details of how these genetic factor work are unclear, but they
may well involve personality factors such as novelty-seeking and harm
avoidance that may influence general vulnerability to drug abuse.
Novelty-seeking may influence how likely someone is to try drugs, whereas
harm avoidance has the opposite effect.

These factors may operate through 'self-control' - low novelty-seeking and
high harm avoidance may make it easy for someone to resist drugs when they
are offered. But another important set of factors are biochemical ones, in
which the body's basic chemistry influences the level of 'rush' achieved
from the drug, how well the drug is tolerated by the body and the severity
of withdrawal. In general, having more severe withdrawal symptoms makes
addition more likely. Environmental factors, especially individual specific
experiences, are also of major importance in how users will react to drug use.

The aim of laboratory genetic studies is to study genes from research
volunteers who have abused opiates in order to gather information on the
genetic causes of drug abuse. This will in turn lead to a detailed
understanding of the role of the biochemical pathways in the body - whether
receptors in the brain, or enzymes in the liver - which influence whether
or not an in individual develops an addiction, and how that addiction is
maintained.

The ultimate aim of this research to use our better understanding the
causes of opiate abuse and dependence, so that better treatments can be
devised.

Treatments for opiate addiction such as methadone, are useful but have
their own problems, including toxicity. Such work may also be useful in
identifying 'high risk' individuals for preventative treatment.

Such treatment could also identify genetic differences in people vulnerable
to addiction which could be fixed by drug treatment. There are two ways
these drugs could work. They could either reduce the pleasurable effects of
the drug, making taking them pointless, or they could reduce the severity
of withdrawal symptoms, making giving them up easier. These could be drugs
aimed at the effects of specific classes of drugs such as opiates. For
example, heroin and codeine do not have much activity in the brain on their
own - they need to be converted to morphine by enzymes in the body to have
their full effect. Drugs which could reduce or prevent this activation, by
blocking specific enzymes in the body, might be useful treatments for
addicts trying to come off the drug, as the 'rush' felt would be blunted.

Similarly, drugs could be aimed at proteins in the body involved in
mediating reward or other pleasurable effects of opiates - such as the
'feel-good' release of the neurotransmitter dopamine in the brain, thus
blunting the desire to take opiates - or at reducing the withdrawal effects
so that stopping taking heroin becomes an easier prospect.

The new scientific evidence on how the genetics of drug addiction works,
and can be managed, opens the prospects that these new drugs will form part
of a framework for the development of new management approaches to problem
drug abuse, alongside cognitive behaviour therapy and other approaches.
While many will highlight the need to consider how such treatments are used
carefully, the overall effect of these developments could help to underpin
a movement from punishment to treatment, giving new tools and options to
addicts who want to end their dependency on drugs.

David Collier is reader in molecular genetics at the Institute of
Psychiatry at King's College London.