Endocannabinoid-mediated synaptic plasticity and substance use disorders, E. Fernandez-Espejo & L. Nunez-Dominguez, 2019

Endocannabinoid-mediated synaptic plasticity and substance use disorders

E. Fernandez-Espejo, L. Nunez-Dominguez
Neurologia, 2019
Copyright © 2019 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
doi : 10.1016/j.nrl.2018.12.004


Drugs impact brain reward circuits, causing dependence and addiction, in a condition currently described as substance use disorders. Mechanisms of synaptic plasticity in these circuits are crucial in the development of addictive behaviour, and endocannabinoids, particularly anandamide and 2-arachidonyl-glycerol, participate in normal neuroplasticity. Substance use disorders are known to be associated with disruption of endocannabinoid-mediated synaptic plasticity, among other phenomena. Endocannabinoids mediate neuroplasticity in the short and the long term. In the short term, we may stress «inhibitory» phenomena, such as depolarisation-induced suppression of inhibition and depolarisation-induced suppression of excitation, and such «disinhibitory» phenomena as long-lasting disinhibition of neuronal activity, particularly in the striatum, and suppression of hippocampal GABA release. Drugs of abuse can also disrupt normal endocannabinoid-mediated long-term potentiation and long-term depression. Endocannabinoids are also involved in the development of drug-induced hypofrontality and sensitisation. In summary, substance abuse causes a disruption in the synaptic plasticity of the brain circuits involved in addiction, with the alteration of normal endocannabinoid activity playing a prominent role. This facilitates abnormal changes in the brain and the development of the addictive behaviours that characterise substance use disorders.

KEYWORDS : Addiction; Adicción; Dependence; Dependencia; Droga; Drug of abuse; Endocannabinoid; Endocannabinoide; Neuroplasticidad; Neuroplasticity