, Volume 236, Issue 1, pp 201–226 | Cite as

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

  • Sabrina F. LisboaEmail author
  • C. Vila-Verde
  • J. Rosa
  • D. L. Uliana
  • C. A. J. Stern
  • L. J. Bertoglio
  • L. B. Resstel
  • F. S. Guimaraes



Aversive 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 methods

The 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.


Currently 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.


Drugs 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.


Stress Anxiety Endocannabinoid Cannabidiol Extinction 



This work was supported by grants from the National Council for Scientific and Technological Development (CNPq), São Paulo Research Foundation (FAPESP), and the National Institute of Science and Translational Medicine (INCT, 465458/2014-9). Figures were created in the Mind the Graph platform (


This work was supported by grants from the National Council for Scientific and Technological Development (CNPq), São Paulo Research Foundation (FAPESP), and the National Institute of Science and Translational Medicine (INCT, 465458/2014-9).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, Medical School of Ribeirão PretoUniversity of São Paulo (FMRP/USP)São PauloBrazil
  2. 2.Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), Medical School of Ribeirão PretoUniversity of São Paulo (USP)Ribeirão PretoBrazil
  3. 3.Department of PharmacologyFederal University of ParanaCuritibaBrazil
  4. 4.Department of PharmacologyFederal University of Santa CatarinaFlorianopolisBrazil

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