Investigations concerning dependence to drug of abuse are of pluridisciplinary nature. It is clear that to understand this complex phenomenon will not be the privilege of one particular level of psychobiological organizations. Whatever the theories, it must be stated that correlational relations exist between behavior, mental states, and brain-neuronal states whatever the transduction principles in cause. An important neglected problem to be investigated concerns the vulnerability presented by some organisms and not by other, either for the search of a drug-stimulus or to repeat the first encounter with the pharmacological agent, potentially a drug of abuse. Such vulnerability corresponds to a neurobiological state considered far from the equilibrium, i.e. homeostasis. Whether the drug, as many other agents, environmental, nutritional, sexual, tends to reduce the imbalance within the neuronal systems is a matter of debate.