Cannabidiol and the corticoraphe circuit in post-traumatic stress disorder

Autor: Maryam S. Vasefi, Claire Alexander
Jazyk: angličtina
Rok vydání: 2021
Předmět:
CBD
Cannabidiol
GPCRs
G-Protein Coupled Receptors
PET
Positron Emission Tomography
DRN
Dorsal Raphe Nucleus
CB2R
Cannabinoid Receptor Type 2
Cannabidiol
Traumatic Stress
Prefrontal cortex
5-HT
Serotonin
General Neuroscience
5-HT2AR
5-HT Receptor Type 2 A
Glutamate receptor
PTSD
PFC
Prefrontal Cortex
ERK1/2
Extracellular Signal-Related Kinases Type 1 or Type 2
medicine.anatomical_structure
GABAergic
NMDAR
N-Methyl-D-aspartate Receptors
CB1R
Cannabinoid Receptor Type 1
psychological phenomena and processes
medicine.drug
RC321-571
mPFC
Medial Prefrontal Cortex
Serotonin
Neurosciences. Biological psychiatry. Neuropsychiatry
SSNRI
Selective Norepinephrine Reuptake Inhibitor
Amygdala
behavioral disciplines and activities
Article
Dorsal raphe nucleus
2-AG
2-arachidonoylglycerol
medicine
fMRI
Functional Magnetic Resonance Imaging
SSRI
Selective Serotonin Reuptake Inhibitor
PFC
DRN and Raphe
business.industry
PTSD
Post-Traumatic Stress Disorder
GABA
Gamma-Aminobutyric Acid
medicine.disease
COVID-19
SARS-CoV-2
digestive system diseases
AEA
Anandamide
nervous system
Extinction (neurology)
5-HT1AR
5-HT Receptor Type 1A
TRPV1
Transient Receptor Potential Vanilloid 1 Channels
business
Hypoactivity
Neuroscience
FAAH
Fatty Acid Amide Hydrolase
Zdroj: IBRO Neuroscience Reports, Vol 11, Iss, Pp 88-102 (2021)
IBRO Neuroscience Reports
ISSN: 2667-2421
Popis: 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.
Highlights • CBD reduces PTSD symptoms via the DRN and corticoraphe circuit. • Acute effects of CBD reduce DRN-amygdala excitatory signaling to lessen the activity disparity between amygdala and mPFC. • Chronic CBD officially resolves mPFC hypoactivity by facilitating 5-HT release from DRN to mPFC. • CBD-facilitated endocannabinoid signaling stabilizes DRN activity and restores mPFC inhibitory control. • Chronically administered CBD acts via the corticoraphe circuit to favor fear extinction over fear memory reconsolidation.
Databáze: OpenAIRE
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