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Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies

  • Lisboa, Sabrina F.1, 2
  • Vila-Verde, C.1, 2
  • Rosa, J.1, 2
  • Uliana, D. L.1, 2
  • Stern, C. A. J.3
  • Bertoglio, L. J.4
  • Resstel, L. B.1, 2
  • Guimaraes, F. S.1, 2
  • 1 University of São Paulo (FMRP/USP), Department of Pharmacology, Medical School of Ribeirão Preto, Av Bandeirantes 3900, Monte Alegre, 14049900, Ribeirão Preto, São Paulo, Brazil , São Paulo (Brazil)
  • 2 University of São Paulo (USP), Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), Medical School of Ribeirão Preto, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 3 Federal University of Parana, Department of Pharmacology, Curitiba, PR, Brazil , Curitiba (Brazil)
  • 4 Federal University of Santa Catarina, Department of Pharmacology, Florianopolis, SC, Brazil , Florianopolis (Brazil)
Published Article
Publication Date
Jan 02, 2019
DOI: 10.1007/s00213-018-5127-x
Springer Nature


RationaleAversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory.Objective and methodsThe objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated.ResultsCurrently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen’s d ≥ 1.0). The brain areas responsible for the abovementioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation.ConclusionDrugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.

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