The therapeutic effectiveness of Cannabidiol (CBD) in treating mental and psychotic disorders and inflammatory ailments has been proven in various clinical studies. Numerous studies have recently indicated the instant antidepressant-like effects of CBD which hints at its potential of being an antidepressant or anti-stress drug. CBD has been found to interact with the same receptors within the brain and nervous system like the antidepressants do. This implies that CBD can assist in the signaling and generation of chemicals that aid to lower symptoms of depression, similar to various antidepressant medications without any “black box warnings.”

This particular study intends to explore the effectiveness of long-term periodic administration of CBD in chronic mild stress (CMS) via oral and intravenous routes and its pharmacokinetics. ICR mice were treated with CBD administered orally and intravenously and the kinetic constants were then determined. A single bolus intravenous injection of CBD led to a half-life of 3.9 h, mean residence time of 3.3 h which denotes the average time a drug remains at the site of action, and oral bioavailability of nearly 8.6%. The antidepressant type impact of periodically administered CBD on the chronic mild stress mouse model are examined. Results revealed that such therapy at a high oral dose of 100 mg/kg CBD or a low intravenous dose of CBD 10 mg per kg, evoked a substantial antidepressant behavioral response following higher mRNA expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus. These findings are anticipated to provide a referral for the production of intravenous antidepressant formulations of CBD.

The salient features of the study were:

  • With pharmacokinetics analyses of CBD, the half-life is 3.9 h, the MRT is 3.3 h. Pharmacokinetics refers to the drug movement into, through and out of the body- the duration of its absorption, distribution, metabolism, bioavailability, and excretion.
  • The oral bioavailability of CBD is approximately 8.6%
  • The low dose of 10mg/kg periodic intravenous CBD presented antidepressant-like impact in chronic mild stress mice model
  • CBD enhances the mRNA expression of Brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus region of the brain.

Brain-derived neurotrophic factor (BDNF) has an integral part in development, synapse remodeling, and reactions to stress and injury. Its abnormal expression has been involved in schizophrenia, a neuropsychiatric ailment in which abnormal neural growth of the hippocampus and prefrontal cortex has been established. The effects of antipsychotic medications used in treating schizophrenia on BDNF mRNA has also been studied in various research and its expression in rats used as an animal model of schizophrenia with neonatal lesions of the ventral hippocampus. Both the antipsychotic drugs administered clozapine and haloperidol decreased BDNF expression in the hippocampus of control rats but did not substantially lower its expression in the prefrontal cortex. THe BDNFmRNA expression was suppressed by the neonatal hippocampal lesion itself within the dentate gyrus and aided to decrease its expression in the prefrontal cortex. In fact, these results highlighted that in contrast to antidepressants, antipsychotics down-regulate BDNFmRNA, and hints that their therapeutic properties are not controlled by activation of this neurotrophin.

Cannabidiol And The Hippocampus

The hippocampus region of the brain performs numerous functions which include mood regulation, fear/stress reactions, and short term memory. People suffering from anxiety disorders and depression were found to possess physically smaller hippocampus. This might be facilitating the disorders themselves.

Hopefully, CBD can influence hippocampus growth and research conducted on stressed-out mice revealed that CBD promoted neurogenesis (regenerated neurons) within the hippocampus. As a result, the mice were observed to have less anxiety after therapy. These findings have unlocked a new understanding of the mechanism of anxiety and depression itself.


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