Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine

Abstract

Rationale

Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial “psychedelic effect,” which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy.

Objective

Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories.

Results

We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition.

Conclusions

Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.

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Notes

  1. 1.

    For “psychedelic effect,” we purposely used a generic classification terminology, given for granted that although the class of psychedelics may have in common some effects (e.g., perceptual distortion), it however includes substances with different mechanisms and patterns of psychoactive effects (including effects on memory processes). Some “psychedelics,” like cannabinoids and ketamine may affect learning and memory. In the present review, we focus on their potential effects on a specific memory process, the reconsolidation of traumatic and appetitive memories.

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Correspondence to Cristiano Chiamulera.

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Fattore, L., Piva, A., Zanda, M.T. et al. Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine. Psychopharmacology 235, 433–445 (2018). https://doi.org/10.1007/s00213-017-4793-4

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Keywords

  • Post-traumatic stress disorders
  • Substance use disorders
  • Reconsolidation
  • Maladaptive memories
  • Cannabinoids
  • Ketamine