Assessing the efficacy of melatonin to curtail benzodiazepine/Z drugabuse

Abstract: The abuse of benzodiazepine (BZP) and Z drugs has become, due to the tolerance and dependence theyproduce, a serious public health problem. Thirty years ago, we demonstrated in experimental animalsthe interaction of melatonin with central BZD receptors, and in 1997 we published the first series ofelderly patients who reduced BZP consumption after melatonin treatment. Almost every single neuron inthe hypothalamic suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system, contains-aminobutyric acid (GABA) and many results in animals point out to a melatonin interaction with GABA-containing neurons. In addition, central-type BZD antagonism, that obliterates GABAAreceptor function,blunted most behavioral effects of melatonin including sleep. Melatonin is involved in the regulation ofhuman sleep. This is supported by the temporal relationship between the rise of plasma melatonin levelsand sleep propensity as well as by the sleep-promoting effects of exogenously administered melatonin.Both meta-analyses and consensus agreements give support to the therapeutic use of melatonin in sleepdisorders. This action is attributed to MT1and MT2melatoninergic receptors localized in the SCN, as wellas in other brain areas. This review discusses available data on the efficacy of melatonin to curtail chronicBZD/Z drug use in insomnia patients. A major advantage is that melatonin has a very safe profile, it isusually remarkably well tolerated and, in some studies, it has been administered to patients at very largedoses and for long periods of time, without any potentiality of abuse. Further studies on this applicationof melatonin are warranted