Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption.
Cristina A J Stern, Lucas Gazarini, Ana C Vanvossen, Antonio W. Zuardi, Ismael Galve-Roperh, Francisco S Guimarães, Reinaldo N Takahashi, Leandro J Bertoglio
European Neuropsychopharmacology June 2015 DOI: 10.1016/j.euroneuro.2015.02.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Interventions | THC CBD |
| Dose | THC 0.3-10 mg/kg, i.p.; sub-effective doses of THC and CBD at a 10 to 1 ratio |
| Duration | Conditioned freezing assessed for over 22 days |
| Measures | conditioned freezing, elevated plus-maze test |
| Topics | CBD Cannabis |
| Keywords | Cb1 receptor Fear memory Medial prefrontal cortex Reconsolidation Δ9-tetrahydrocannabinol |
| Key points | THC disrupted reconsolidation of a contextual fear memory, reducing conditioned freezing for over 22 days via CB1 receptors in the prelimbic medial prefrontal cortex, dependent on memory retrieval. Sub-effective doses of THC plus CBD also attenuated fear memory maintenance additively at a 10:1 ratio, without affecting anxiety-related behaviors or locomotor activity. |
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.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 11
- Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age Frontiers in Immunology September 21, 2018
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial PLoS One March 17, 2021
- Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. Pharmacology & Therapeutics November 1, 2022
- Ayahuasca Impairs Fear Memory Reconsolidation and Promotes Rapid Structural Plasticity in the Hippocampus and Prelimbic Cortex. Molecular Neurobiology October 12, 2026
and 6 more in the library
Cites 12
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- Mitigation of post‐traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence Drug Testing and Analysis June 26, 2012
- Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clinical drug investigation August 2014
- Dissociation of the pharmacological effects of THC by mTOR blockade. Neuropsychopharmacology June 2013
- Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being Psychological Medicine February 1, 2012
and 7 more in the library