Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. 2010

Abir T El-Alfy, and Kelly Ivey, and Keisha Robinson, and Safwat Ahmed, and Mohamed Radwan, and Desmond Slade, and Ikhlas Khan, and Mahmoud ElSohly, and Samir Ross
Pharmacology Department, School of Pharmacy, University of Mississippi, University, MS 38677, USA. aalfy2001@olemiss.edu

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.

UI MeSH Term Description Entries
D007035 Hypothermia Lower than normal body temperature, especially in warm-blooded animals. Hypothermia, Accidental,Accidental Hypothermia,Accidental Hypothermias,Hypothermias,Hypothermias, Accidental
D008297 Male Males
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D002185 Cannabidiol Compound isolated from Cannabis sativa extract. 1,3-Benzenediol, 2-(3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl)-5-pentyl-, (1R-trans)-,Epidiolex
D002186 Cannabinoids Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL. Cannabinoid
D002188 Cannabis The plant genus in the Cannabaceae plant family, Urticales order, Hamamelidae subclass. The flowering tops are called many slang terms including pot, marijuana, hashish, bhang, and ganja. The stem is an important source of hemp fiber. Bhang,Ganja,Hashish,Hemp,Cannabis indica,Cannabis sativa,Hemp Plant,Marihuana,Marijuana,Bhangs,Cannabi,Ganjas,Hashishs,Hemp Plants,Hemps,Plant, Hemp,Plants, Hemp
D002375 Catalepsy A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions. Cerea Flexibilitas,Flexibility, Waxy,Anochlesia,Anochlesias,Catalepsies,Flexibilitas, Cerea,Flexibilities, Waxy,Waxy Flexibilities,Waxy Flexibility
D003863 Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. Depressive Symptoms,Emotional Depression,Depression, Emotional,Depressive Symptom,Symptom, Depressive
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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