DESPOTIC (Derive the Energetics and SPectra of Optically Thick Interstellar Clouds), written in Python, represents optically thick interstellar clouds using a one-zone model and calculates line luminosities, line cooling rates, and in restricted cases line profiles using an escape probability formalism. DESPOTIC calculates clouds' equilibrium gas and dust temperatures and their time-dependent thermal evolution. The code allows rapid and interactive calculation of clouds' characteristic temperatures, identification of their dominant heating and cooling mechanisms, and prediction of their observable spectra across a wide range of interstellar environments.