We elaborate here a heuristic framework based on the behavioural and imaging phenotypes of addiction as three stages linked by three functional domains that are mediated by three major neurobiological circuits (basal ganglia, extended amygdala, and prefrontal cortex) and numerous microcircuits of neuroplasticity. We outline 18 neurochemically defined mini circuits that can independently or interactively load the outputs of the major common neurobiological circuits to produce incentive salience and compulsive-like habits, negative emotional states of low reward and excessive stress, and compromised executive function. Identification of these molecular and neurochemical loads on the circuitry provides key information about vulnerability, resilience, treatment, and recovery from addiction, as well as information on how different drugs of abuse enter the overall addiction cycle. Non-drug addictions, such as pathological gambling, have a similar behavioural phenotype that fits into the three-stage cycle. Preliminary imaging data also suggest common neurobiology. Key questions that remain are what genetic factors load these mini circuits, how the environment conveys epigenetic influences on these circuits, and how these circuits recover or do not recover with abstinence and treatment. Resolving these
