The emetic liability of anticancer agents will be determined in a cat model by oscillographically recording the physiological forces which produce the response. This documentation of the incidence of vomiting, its latency, duration and repetitiveness will provide the basis for establishing standard "emetic profiles" for each anticancer agent studied. Promising new drugs such as delta-9-tetrahydrocannabinol (THC) and other naturally occuring and synthetic cannabinoids will be tested for their ability to modify these emetic profiles. Emphasis will be placed on testing cannabinoids which produce behavioral effects which differ in character or intensity from those produced by TCH itself. These will include cannabidiol (CBD), delta-8-THC and 11-hydroxy-delta-9-THC. This study will devote effort towards correlating the bioavailability of the various cannabinoids, when given in various formulations and by various routes, with their antiemetic efficacy. In collaboration with Dr. James C. Cradock and Dr. Karl P. Flora, Division of Cancer Treatment, NCI, the antiemetic effectiveness of cannobinoids given by the oral, i.v. and i.m. depot routes will be related to circulating plasma concentrations. In addition to the cannabinoids, other agents with reported antiemetic activity will be studied and compared. These will include metoclopramide, droperidol, domperidone, various steroids and the narcotics. Studies on the mechanisms by which these psychoactive compounds exert their antiemetic effects will entail classical neurophysiological manipulations of the nervous system. Lesioning and truncation procedures will be incorporated as well as electrophysical interrogation of the functional interaction between the medullary chemoreceptor trigger zone for emesis, located in the area postrema and the vomiting center situated in the subadjacent reticular formation.