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Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

Abir T. El-Alfy, Kelly Ivey, Keisha Robinson, Safwat A Ahmed, Mohamed O. Radwan, Desmond Slade, Ikhlas A Khan, Mahmoud A. Elsohly, Samir Ross

Pharmacology, Biochemistry, and Behavior June 2010 DOI: 10.1016/j.pbb.2010.03.004 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical experimental study Peer reviewed
Population Mice
Interventions Delta(9)-THC Delta(8)-THC Cannabigerol (CBG) Cannabinol (CBN) Cannabichromene (CBC) Cannabidiol (CBD)
Dose Delta(9)-THC and Delta(8)-THC: 1.25, 2.5, 5 mg/kg i.p.; CBG and CBN: up to 80 mg/kg; CBC: 20, 40, 80 mg/kg; CBD: 200 mg/kg
Measures Forced swim test (FST), Tail suspension test (TST), Mouse tetrad assay
Topics Cannabis
Key findings Delta(9)-THC at 2.5 mg/kg and CBC at 20, 40, and 80 mg/kg produced antidepressant-like effects in mice, while CBG and CBN did not up to 80 mg/kg.

Abstract

The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (p<0.05) in the FST. The cannabinoids cannabigerol (CBG) and cannabinol (CBN) did not produce antidepressant-like actions up to 80 mg/kg in the mouse FST, while cannabichromene (CBC) and cannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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