Effects of cannabinoid drugs on aversive and rewarding drug-associated memory extinction and reconsolidation.

Posttraumatic stress and drug use disorders may stem from aberrant memory formation. As the endocannabinoid (eCB) system has a pivotal role in emotional memory processing and related synaptic plasticity, here we seek to review and discuss accumulating evidence on how and where in the brain interventions targeting the eCB system would attenuate outcomes associated with traumatic events and/or drug addiction through memory extinction facilitation or memory reconsolidation disruption. Currently available data from mouse, rat, monkey and healthy human studies investigating the effects of cannabinoid drugs on the extinction and reconsolidation of aversive memories are more consistent than those related to rewarding drug-associated memories. Interventions able to attenuate aversive memories by extinction facilitation or reconsolidation disruption have boosted the anandamide-induced activation of cannabinoid type-1 (CB₁) receptors. A still limited number of studies report that CB₁ activation could also be effective in facilitating the extinction or disrupting the reconsolidation of rewarding drug-associated memories. The reinstatement of extinguished drug memories (relapse) is reduced by CB₁ receptor antagonism. The cannabidiol has shown to be effective in any of the aforementioned cases, albeit its mechanism of action is not fully understood. Brain areas in which cannabinoid drugs induce these effects include the prefrontal cortex, amygdala, hippocampus, and/or nucleus accumbens. The potential role of 2-arachidonoylglycerol (2-AG) and cannabinoid type-2 (CB₂) receptors in emotional memory extinction and reconsolidation is currently under investigation. Overall, preclinical data support a closer look into certain cannabinoid drugs owing to their safety and potential therapeutic value against stress-related and drug use disorders.

Copyright © 2017. Published by Elsevier Ltd.