The goal of this project is to determine whether our preliminary findings of significant associations between low circulating levels of cholesterol and of some polyunsaturated fatty acids (PUFAs) and the relapse rate of detoxified cocaine addicts can be replicated in a larger population sample. Attempts will be also made to determine whether some factors such as poor nutritional habits contribute to the presence of altered cholesterol values or fatty acid profiles in some patients. The role of cholesterol and PUFAs has not been investigated in addictive disorders but our data can be understood in light of recent literature suggesting the existence of associations between low cholesterol levels and a number of psychiatric disorders including depression, suicide and violence. Cholesterol does not cross the blood-brain barrier but it has been suggested that it could be a marker for changes in PUFAs. There is mounting evidence that low levels of some PUFAs are also associated with a variety of psychiatric disorders. Some PUFAs are main components of neuronal synaptic membranes and influence neuronal function. Preclinical studies have demonstrated that PUFAs influence the function of dopamine and 5-HT that play a role in reward mechanisms. One hundred and twenty cocaine addicts admitted to a Substance Abuse Inpatient Unit will be studied. While on the ward, they will undergo assessments of cholesterol and its subfractions and of the entire fatty acids series. After discharge, they will be transferred to a Substance Abuse clinic where follow-up assessments will be conducted for 12 months. The primary outcome measures will be time to relapse as determined monthly by qualitative urine and selfreported use. Psychosocial functioning, cocaine craving and dietary intake will also be monitored monthly. Cholesterol and fatty acids will be determined every 3 months. If our preliminary findings are confirmed, the use of fatty acids supplements or changes in dietary habits could have a significant potential in the prevention of relapse in a subgroup of cocaine addicts.