Skip to main content
Canna~Fangled Abstracts

Cannabidiol induces antidepressant and anxiolytic-like effects in experimental type-1 diabetic animals by multiple sites of action

By January 19, 2021No Comments
These findings indicated a therapeutic potential for CBD in the treatment of depression/anxiety associated with diabetes pointing out a complex intrinsic mechanism in which 5-HT1A, CB1, and/or CB2 receptors are differently recruited.
2021 Jan 19.

doi: 10.1007/s11011-020-00667-3.

Online ahead of print.
Yane Costa Chaves 1, Karina Genaro 2 3, José Alexandre Crippa 4 5, Joice Maria da Cunha 1 2, Janaína Menezes Zanoveli 6 7
Affiliations 

Abstract

Cannabidiol (CBD), a phytocannabinoid compound, presents antidepressant and anxiolytic-like effects in the type-1 diabetes mellitus(DM1) animal model. Although the underlying mechanism remains unknown, the type-1A serotonin receptor (5-HT1A) and cannabinoids type-1 (CB1) and type-2 (CB2) receptors seem to play a central role in mediating the beneficial effects on emotional responses. We aimed to study the involvement of these receptors on an antidepressant- and anxiolytic-like effects of CBD and on some parameters of the diabetic condition itself. After 2 weeks of the DM1 induction in male Wistar rats by streptozotocin (60 mg/kg; i.p.), animals were treated continuously for 2-weeks with the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg, i.p.), CB1 antagonist AM251 (1 mg/kg i.p.) or CB2 antagonist AM630 (1 mg/kg i.p.) before the injection of CBD (30 mg/kg, i.p.) or vehicle (VEH, i.p.) and then, they were submitted to the elevated plus-maze and forced swimming tests. Our findings show the continuous treatment with CBD improved all parameters evaluated in these diabetic animals. The previous treatment with the antagonists – 5-HT1A, CB1, or CB2 – blocked the CBD-induced antidepressant-like effect whereas only the blockade of 5-HT1A or CB1 receptors was able to inhibit the CBD-induced anxiolytic-like effect. Regarding glycemic control, only the blockade of CB2 was able to inhibit the beneficial effect of CBD in reducing the glycemia of diabetic animals. These findings indicated a therapeutic potential for CBD in the treatment of depression/anxiety associated with diabetes pointing out a complex intrinsic mechanism in which 5-HT1A, CB1, and/or CB2 receptors are differently recruited.

 

Keywords: AM251, AM630, Elevated plus maze, Forced swimming test, Streptozotocin, WAY100635

References

    1. Abdelwahed OM, Tork OM, Gamal El Din MM et al (2018) Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain visfatin. Brain Res Bull 139:67–80 – PubMed – DOI – PMC
    1. Adeyemi DO, Adewole OS (2019) Hibiscus sabdariffa renews pancreatic β-cells in experimental type 1 diabetic model rats. Morphologie 103:80–93 – PubMed – DOI – PMC
    1. Aftab A, Bhat C, Gunzler D et al (2018) Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: findings from an interventional randomized controlled trial. Int J Psychiatry Med 53:126–140 – PubMed – DOI – PMC
    1. Aghazadeh Tabrizi M, Baraldi PG, Ruggiero E et al (2016) Synthesis and structure activity relationship investigation of triazolo[1,5-a]pyrimidines as CB2 cannabinoid receptor inverse agonists. Eur J Med Chem 113:11–27 – PubMed – DOI – PMC
    1. Anderson RJ, Freedland KE, Clouse RE et al (2001) The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24:1069–1078 – PubMed – DOI – PMC

Leave a Reply