Comparison between cannabidiol and sertraline for the modulation of post-traumatic stress disorder-like behaviors and fear memory in mice

Han, Xiao; Song, Xiankui; Song, Dake; Xie, Guanbo; Guo, Hongyan; Wu, Ning; Li, Jin

doi:10.1007/s00213-022-06132-6

Cited by 15 publications

(11 citation statements)

References 83 publications

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“…Our finding that cannabidiol reduced learned fear expression acutely during delayed or immediate extinction broadly agrees with previous results on cannabidiol regulation of contextual and cued fear expression. Studies have shown that systemic cannabidiol treatment reduces contextual fear expression [ 10 , 11 , 12 , 13 ]. We also showed previously that cannabidiol reduces the expression of baseline and cued fear during delayed extinction [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cannabidiol is the main non-psychotropic constituent of cannabis and has anxiolytic potential [ 6 , 7 , 8 , 9 ]. Acute cannabidiol treatment reduces the expression of learned fear [ 6 , 10 , 11 , 12 , 13 ]. Cannabidiol also enhances fear extinction to facilitate the reduction of learned fear expression [ 12 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance

Papagianni

Warren

Cassaday

et al. 2022

IJMS

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Cannabidiol, the main non-psychotropic constituent of cannabis, has potential as a treatment for anxiety-related disorders since it reduces learned fear expression and enhances fear extinction. The return of fear over time after successful extinction and stress-induced extinction resistance are potential barriers to the treatment of these disorders with extinction-based psychological therapy. In two experiments using rats subjected to auditory fear conditioning, we determined the effects of systemic cannabidiol treatment on (1) delayed extinction and later spontaneous fear recovery, and (2) extinction resistance caused by immediate extinction (the immediate extinction deficit (IED)). In Experiment 1, cannabidiol was given before delayed extinction occurring 24 h after conditioning, with extinction recall and spontaneous fear recovery tested drug-free 1 and 21 days after extinction, respectively. We found that cannabidiol had no effect on extinction recall but it prevented spontaneous fear recovery. In Experiment 2, the IED procedure was first validated, with immediate extinction occurring 30 min after conditioning. We confirmed that immediate extinction impaired extinction recall, compared to delayed extinction. Next, cannabidiol was given before immediate or no extinction, with extinction recall tested drug-free the next day. We found that cannabidiol rescued the IED, which did not involve effects on fear memory consolidation. In summary, cannabidiol prevented spontaneous fear recovery after delayed extinction and ameliorated extinction resistance caused by immediate extinction. Although the pharmacological mechanisms underlying these effects remain to be determined, our results add to evidence indicating that cannabidiol might prove useful as an adjunct for potentiating the psychological treatment of anxiety-related disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance

Papagianni

Warren

Cassaday

et al. 2022

IJMS

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“…Long-term oral CBD treatment reduced freezing in the cue test of all females, regardless of the genotype. Although it is well established that acute systemic CBD can impair fear memory consolidation ( Han et al, 2022 ; Shallcross et al, 2019 ; review: Stern et al, 2018 ), including in female mice ( Montoya et al, 2020 ), effects of chronic CBD on fear memory have had limited investigation, and chronic CBD does not affect fear memory acquisition ( Cheng et al, 2014a ; 2014c ). Considering CBD-induced differences in freezing were very limited in this study, future research should consider evaluating the effects of long-term CBD on fear learning in female mice.…”

Section: Discussionmentioning

confidence: 99%

Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model

Chesworth

Cheng²,

Staub³

et al. 2022

Front. Pharmacol.

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Cannabidiol is a promising potential therapeutic for neurodegenerative diseases, including Alzheimer’s disease (AD). Our laboratory has shown that oral CBD treatment prevents cognitive impairment in a male genetic mouse model of AD, the amyloid precursor protein 1 x presenilin 1 hemizygous (APPxPS1) mouse. However, as sex differences are evident in clinical populations and in AD mouse models, we tested the preventive potential of CBD therapy in female APPxPS1 mice. In this study, 2.5-month-old female wildtype-like (WT) and APPxPS1 mice were fed 20 mg/kg CBD or a vehicle via gel pellets daily for 8 months and tested at 10.5 months in behavioural paradigms relevant to cognition (fear conditioning, FC; cheeseboard, CB; and novel object recognition test, NORT) and anxiety-like behaviours (elevated plus maze, EPM). In the CB, CBD reduced latencies to find a food reward in APPxPS1 mice, compared to vehicle-treated APPxPS1 controls, and this treatment effect was not evident in WT mice. In addition, CBD also increased speed early in the acquisition of the CB task in APPxPS1 mice. In the EPM, CBD increased locomotion in APPxPS1 mice but not in WT mice, with no effects of CBD on anxiety-like behaviour. CBD had limited effects on the expression of fear memory. These results indicate preventive CBD treatment can have a moderate spatial learning-enhancing effect in a female amyloid-β-based AD mouse model. This suggests CBD may have some preventive therapeutic potential in female familial AD patients.

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“…Long-term oral CBD treatment reduced freezing in the cue test of all females regardless of genotype. While it is well-established that acute systemic CBD can impair fear memory consolidation ( Stern et al, 2018 ; Shallcross et al, 2019 ; Han et al, 2022 ), including in female mice ( Montoya et al, 2020 ), effects of chronic CBD on fear memory have had limited investigation and chronic CBD does not appear to affect fear memory acquisition ( Cheng et al, 2014 , 2014c ). Considering CBD-induced differences in freezing were very limited in this study, future research should consider evaluating the effects of long-term CBD on fear learning in more detail.…”

Section: Discussionmentioning

confidence: 99%

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

Visini

Brown

Weston–Green

et al. 2022

Front. Cell. Neurosci.

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Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it’s potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous (Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains.

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Comparison between cannabidiol and sertraline for the modulation of post-traumatic stress disorder-like behaviors and fear memory in mice

Cited by 15 publications

References 83 publications

Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance

Cannabidiol Prevents Spontaneous Fear Recovery after Extinction and Ameliorates Stress-Induced Extinction Resistance

Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model

The effects of preventative cannabidiol in a male neuregulin 1 mouse model of schizophrenia

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