Though usually initiated through social reinforcement, self-administration of psychoactive drugs (SAPD) is soon reinforced pharmacologically through suppression (by each successive dose) of a homeostatic need generated by successive central counteradaptive changes (CCCs) that develop unconditionally in response to the initial (receptor site) actions of such drugs and their "reflex" consequences (signs of drug effects). Temporal contiguity between pharmacological reinforcement and recurring exteroceptive and interoceptive stimuli (CCs) results in increasing probability of occurrence of both CCCs and SAPD in the presence of the CSs (appetitive conditioning), even long after detoxification (DTX). To prevent relapse, both conditioned CCCs (conditioned abstinence, CA) and conditioned SAPD should be actively extinguished after DTX by elicitation of CA and programmed SAPD under conditions preventing pharmacological reinforcement. Associated psychopathologies and previous state-dependent learning may pose problems in rehabilitation.