Over the 75-year lifetime of the British Pharmacological Society there has been an enormous
expansion in our understanding of how opioid drugs act on the nervous system, with much of this
effort aimed at developing powerful analgesic drugs devoid of the side effects associated with
morphine – the Holy Grail of opioid research. At the molecular and cellular level multiple opioid
receptors have been cloned and characterised, their potential for oligomerisation determined, a large
family of endogenous opioid agonists has been discovered, multiple second messengers identified and
our understanding of the adaptive changes to prolonged exposure to opioid drugs (tolerance and
physical dependence) enhanced. In addition, we now have greater understanding of the processes by
which opioids produce the euphoria that gives rise to the intense craving for these drugs in opioid
addicts. In this article, we review the historical pathway of opioid research that has led to our current
state of knowledge.
British Journal of Pharmacology (2006) 147, S153–S162. doi:10.1038/sj.bjp.0706435

holy_grail_of_opiates Feb 2010