The knowledge of the chemical transformations induced by heat is of fundamental significance for any chemical compound. The alkaloids and related substances represent a important class of compounds that have played an important role in the development of modern medicine. However, the abuse of certain members of this class (eg. cocaine and heroin) is creating a substantial health problem. For a variety of reasons, the use of heat as a drug delivery system is becoming increasingly common (eg "crack smoking"). In order to completely evaluate the health problem associated with abused substances, it is important to understand the role heat may play in altering their chemical composition. Our approach to this problem will be to study the thermal chemistry of the alkaloids in the gas phase. Because the drug delivery also involves the gas phase, these studies will give insight into the chemical alteration of these drugs that may be occurring during "crack smoking" as well as giving insight into the more complex chemical processes that may be occurring in the condensed phase. Our preliminary studies on (-)-cocaine demonstrate that it is thermally labile at 550 degreesC undergoing a dramatic structural transformation into three products unrelated to cocaine. These preliminary studies are very encouraging indicating that the thermal reactions of alkaloids is not a "hopelessly complex problem." We plan study the thermolysis of cocaine under different environmental conditions and to extend these studies to other alkaloids associated with cocaine. The results of these studies on the tropane alkaloids will provide important data on their thermal reactions and products. This knowledge along with biological date is essential for a complete understanding the impact of using heat as a drug delivery system. Once the thermal chemistry of cocaine and related alkaloids is completed we will use the experience to expand our studies and related alkaloids. Because this research program is aimed at a basic understanding of the thermal reactions of the alkaloids the results may have an impact on problems related to cocaine other than those associated with drug delivery. In particular, we believe that the results of our thermal studies suggest new methods for the preparation of compounds of biological interest. Our preliminary studies have already sugggested a method for the preparation of the unconjugated isomer of methyl ecgonidine, an important alkaloid related to cocaine that has never been characterized or its biological properties studied.