Cannabidiol and the corticoraphe circuit in post-traumatic stress disorder.
| Autor: | Alexander C; Department of Biology, Lamar University, Beaumont, TX 77710, USA., Vasefi M; Department of Biology, Lamar University, Beaumont, TX 77710, USA. |
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| Jazyk: | angličtina |
| Zdroj: | IBRO neuroscience reports [IBRO Neurosci Rep] 2021 Aug 21; Vol. 11, pp. 88-102. Date of Electronic Publication: 2021 Aug 21 (Print Publication: 2021). |
| DOI: | 10.1016/j.ibneur.2021.08.001 |
| Abstrakt: | Post-Traumatic Stress Disorder (PTSD), characterized by re-experiencing, avoidance, negative affect, and impaired memory processing, may develop after traumatic events. PTSD is complicated by impaired plasticity and medial prefrontal cortex (mPFC) activity, hyperactivity of the amygdala, and impaired fear extinction. Cannabidiol (CBD) is a promising candidate for treatment due to its multimodal action that enhances plasticity and calms hyperexcitability. CBD's mechanism in the mPFC of PTSD patients has been explored extensively, but literature on the mechanism in the dorsal raphe nucleus (DRN) is lacking. Following the PRISMA guidelines, we examined current literature regarding CBD in PTSD and overlapping symptomologies to propose a mechanism by which CBD treats PTSD via corticoraphe circuit. Acute CBD inhibits excess 5-HT release from DRN to amygdala and releases anandamide (AEA) onto amygdala inputs. By first reducing amygdala and DRN hyperactivity, CBD begins to ameliorate activity disparity between mPFC and amygdala. Chronic CBD recruits the mPFC, creating harmonious corticoraphe signaling. DRN releases enough 5-HT to ameliorate mPFC hypoactivity, while the mPFC continuously excites DRN 5-HT neurons via glutamate. Meanwhile, AEA regulates corticoraphe activity to stabilize signaling. AEA prevents DRN GABAergic interneurons from inhibiting 5-HT release so the DRN can assist the mPFC in overcoming its hypoactivity. DRN-mediated restoration of mPFC activity underlies CBD's mechanism on fear extinction and learning of stress coping. Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2021 The Authors. Published by Elsevier Ltd on behalf of International Brain Research Organization.) |
| Databáze: | MEDLINE |
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