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. 2015 Jun;25(6):958-65.
doi: 10.1016/j.euroneuro.2015.02.001. Epub 2015 Feb 16.

Δ9-Tetrahydrocannabinol Alone and Combined With Cannabidiol Mitigate Fear Memory Through Reconsolidation Disruption

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Δ9-Tetrahydrocannabinol Alone and Combined With Cannabidiol Mitigate Fear Memory Through Reconsolidation Disruption

Cristina A J Stern et al. Eur Neuropsychopharmacol. .

Abstract

Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level. We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation. Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples. Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation. Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients.

Keywords: CB1 receptor; Cannabidiol; Fear memory; Medial prefrontal cortex; Reconsolidation; Δ(9)-Tetrahydrocannabinol.

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