Medicinal cannabis oil improves anxiety-like and depressive-like behaviors in CCS mice via the BDNF/TRPC6 signaling pathway

Behav Brain Res. 2024 Jun 5:467:115005. doi: 10.1016/j.bbr.2024.115005. Epub 2024 Apr 17.


Background: Post-traumatic stress disorder (PTSD) refers to a chronic impairing psychiatric disorder occurring after exposure to the severe traumatic event. Studies have demonstrated that medicinal cannabis oil plays an important role in neuroprotection, but the mechanism by which it exerts anti-PTSD effects remains unclear.

Methods: The chronic complex stress (CCS) simulating the conditions of long voyage stress for 4 weeks was used to establish the PTSD mice model. After that, behavioral tests were used to evaluate PTSD-like behaviors in mice. Mouse brain tissue index was detected and hematoxylin-eosin staining was used to assess pathological changes in the hippocampus. The indicators of cell apoptosis and the BDNF/TRPC6 signaling activation in the mice hippocampus were detected by western blotting or real-time quantitative reverse transcription PCR experiments.

Results: We established the PTSD mice model induced by CCS, which exhibited significant PTSD-like phenotypes, including increased anxiety-like and depression-like behaviors. Medicinal cannabis oil treatment significantly ameliorated PTSD-like behaviors and improved brain histomorphological abnormalities in CCS mice. Mechanistically, medicinal cannabis oil reduced CCS-induced cell apoptosis and enhanced the activation of BDNF/TRPC6 signaling pathway.

Conclusions: We constructed a PTSD model with CCS and medicinal cannabis oil that significantly improved anxiety-like and depressive-like behaviors in CCS mice, which may play an anti-PTSD role by stimulating the BDNF/TRPC6 signaling pathway.

Keywords: BDNF; Chronic complex stress; Medicinal cannabis oil; Post-traumatic stress disorder; TRPC6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety* / drug therapy
  • Anxiety* / metabolism
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor* / drug effects
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Depression* / drug therapy
  • Depression* / metabolism
  • Disease Models, Animal*
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Male
  • Medical Marijuana / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Plant Oils / administration & dosage
  • Plant Oils / pharmacology
  • Signal Transduction* / drug effects
  • Stress Disorders, Post-Traumatic* / drug therapy
  • Stress Disorders, Post-Traumatic* / metabolism
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism
  • TRPC6 Cation Channel* / metabolism


  • Brain-Derived Neurotrophic Factor
  • Bdnf protein, mouse
  • TRPC6 Cation Channel
  • Trpc6 protein, mouse
  • Medical Marijuana
  • Plant Oils