A multistep general theory of transition to addiction.

Pier Vincenzo Piazza, Véronique Deroche-Gamonet
Psychopharmacology. 2013-08-21; 229(3): 387-413
DOI: 10.1007/s00213-013-3224-4

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1. Psychopharmacology (Berl). 2013 Oct;229(3):387-413. doi:
10.1007/s00213-013-3224-4. Epub 2013 Aug 21.

A multistep general theory of transition to addiction.

Piazza PV(1), Deroche-Gamonet V.

Author information:
(1)Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862,
INSERM, 146 rue Léo Saignat, Bordeaux, 33076, France,

Comment in
Psychopharmacology (Berl). 2014 Oct;231(19):3921-2.
Psychopharmacology (Berl). 2014 Oct;231(19):3923-7.
Psychopharmacology (Berl). 2014 Oct;231(19):3911-7.
Psychopharmacology (Berl). 2014 Oct;231(19):3929-37.
Psychopharmacology (Berl). 2014 Oct;231(19):3919-20.
Psychopharmacology (Berl). 2014 Oct;231(19):3909-10.

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.

DOI: 10.1007/s00213-013-3224-4
PMCID: PMC3767888
PMID: 23963530 [Indexed for MEDLINE]

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