A multistep general theory of transition to addiction

Abstract

Background: Several theories propose alternative explanations for drug addiction.

Objectives: We propose a general theory of transition to addiction that synthesizes knowledge generated in the field of addiction into a unitary explanatory frame.

Major principles of the theory: Transition to addiction results from a sequential three-step interaction between: (1) individual vulnerability; (2) degree/amount of drug exposure. The first step, sporadic recreational drug use is a learning process mediated by overactivation of neurobiological substrates of natural rewards that allows most individuals to perceive drugs as highly rewarding stimuli. The second, intensified, sustained, escalated drug use occurs in some vulnerable individuals who have a hyperactive dopaminergic system and impaired prefrontal cortex function. Sustained and prolonged drug use induces incentive sensitization and an allostatic state that makes drugs strongly wanted and needed. Habit formation can also contribute to stabilizing sustained drug use. The last step, loss of control of drug intake and full addiction, is due to a second vulnerable phenotype. This loss-of-control-prone phenotype is triggered by long-term drug exposure and characterized by long-lasting loss of synaptic plasticity in reward areas in the brain that induce a form of behavioral crystallization resulting in loss of control of drug intake. Because of behavioral crystallization, drugs are now not only wanted and needed but also pathologically mourned when absent.

Conclusions: This general theory demonstrates that drug addiction is a true psychiatric disease caused by a three-step interaction between vulnerable individuals and amount/duration of drug exposure.

Fig. 1

Summary of the phases and processes of transition to addiction. Transition to addiction is a progression of three consecutive phases: (1) Recreational, sporadic (ReS) drug use, in which drug intake is moderate and sporadic and still one among many recreational activities of the individual. (2) Intensified, sustained, escalated (ISuE) drug use, in which drug intake intensifies and is now sustained and frequent and becomes the principal recreational activity of the individual; although some decreased societal and personal functioning start appearing, behavior is still largely organized. (3) Loss of control (LoC) of drug use and full addiction that results in disorganization of the addict’s behavior; drug-devoted activities are now the principal occupations of the individual. The three phases are consecutive but independent: entering one phase is necessary but not sufficient to progress toward the next phase, because specific individual vulnerabilities are needed. The first phase (ReS) occurs in most individuals (use prone); drugs overactivate the same substrates of natural rewards and therefore are perceived as extremely salient and likable stimuli. The second phase (ISuE) occurs in a vulnerable subset of individuals (escalation prone) because of quantitative differences in the activity of the brain reward-related system, which increases the motivational effects of the drug, for example, a hyperactive (sensitized) dopaminergic system and an impaired prefrontal cortex. The ISuE phase is then stabilized by additional drug-induced adaptations, inducing an allostatic state that makes drugs not only strongly wanted but also needed in order for the individual to function normally and, in certain cases, by habit formation. The last phase (LoC) leads to full addiction and is due to a second vulnerable phenotype that we term loss of control prone. This phenotype is characterized by a persistent loss of long-term depression of synaptic transmission (LTD) in reward-related brain areas, which can induce a crystallization of behavior around drug-taking, resulting in losing control of drug intake. In the addicted state, the presence of the drug is not only needed to function normally, as at the end of the ISuE phase, but its absence is experienced as an irreplaceable loss and strongly pathologically mourned. When the individual goes from liking drugs to pathologically mourning them when they are not available, the process of transition to addiction is complete