[Immunomodulator as medicine for morphine and cocaine dependence. Especially effect of LPS]

The majority of medicines developed for narcotic and stimulant dependence were agonists or antagonists of neurotransmitters and their receptors. Recently it has been shown that the nervous system, the endocrine system and the immune system are regulated by mutual interaction. The nervous system and the endocrine system are influenced by an immunomodulator, and the immune system is regulated by a neurotransmitter. In this report, medicines for morphine and cocaine dependence are first surveyed and then medicines for drug dependence through the activation of the immune system are introduced including our results which show the effect of macrophage activator such as LPS on morphine and cocaine dependence. The LPS purified from Pantoea agglomerans showed a relief effect on physical dependence of morphine and psychic dependence of cocaine, while it induced endogenous opioid, beta-endorphin. The induction of beta-endorphin was recognized to be in synchrony with the time course and dose response of the relief of dependence. These data suggest the participation of endogenous opioid such as beta-endorphin induced by LPS after the activation of macrophage leading to the relief of morphine and cocaine dependence.