Beat the Bottle by blocking "pub-stance" P receptor

17 February 2008
Posted by Chris Smith.

Scientists have successfully tested a new compound that can help alcoholics to beat their cravings.

In a paper in this week's edition of the journal Science, Maryland-based NIH researcher and lead author David George and his colleagues randomised 50 recently-detoxified alcoholics aged between 21 and 65 to receive either the new drug, called LY686017, or a placebo.  The patients were monitored as hospital inpatients over several weeks and their alcohol cravings and other behavioural measures were assessed by medical staff. The results showed significant improvements in addiction-symptoms, including self-reported craving, amongst the patients receiving the active drug compared with the placebo, but without major side effects.

The drug works by blocking a chemical docking station known as the neurokinin 1 receptor (NK1R).  This receptor, together with the chemical that activates it, Substance P, is highly expressed in brain areas linked to reward and addiction.  Studies in mice showed that genetically knocking out the receptor causes animals to consume less alcohol, suggesting that drugs capable of blocking its action in humans might achieve the same effect, which was the thrust of the present study.  But to find out how the drug was working in the human subjects, the researchers also brain-scanned them as they were shown images of alcoholic and non-alcoholic beverages.

Predictably, alcoholics in the placebo arm of the study showed strong brain responses to images of alcoholic drinks, whilst the responses in patients on the new agent were much reduced.  In particular, images of alcohol shown to the treated patients elicited much less activity in the subjects' insula cortices, the parts of the nervous system known to be associated with craving.  Further clinical trials will be needed to determine the long term effectiveness of this kind of treatment, and how it should be slotted into therapy to help alcoholics to recover, but the impact could be highly significant, particularly since alcohol accounts for over 4% of the global disease burden.

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