The key component for treating schizophrenia is antipsychotic drugs (APDs), which are highly effective in treating its positive symptoms like hallucinations, but offers marginal benefits for managing the negative symptoms, such as social withdrawal and cognitive deficits. Cannabidiol (CBD), a component of the hemp plant, contains anti inflammatory and antipsychotic qualities and improves cognition. Clinical studies have exhibited that

CBD improves cognition in different preclinical model of cognitive impairment, consisting of models of neurodegenerative (Alzheimer’s disease), neuropsychiatric (schizophrenia), neuro-inflammatory (meningitis and cerebral malaria) and neurological disorders (brain ischemia). The potential of CBD to regain cognition in several studies of impairment, warrants further investigation.

In this particular study the impact of chronic CBD therapy on glutamatergic, GABAergic, and endocannabinoid signalling markers in brain areas involved in social behavior and cognitive activity, including the prefrontal cortex (PFC) and hippocampus (HPC) is investigated. Recent evidences have revealed that treating with the non-psychoactive phytocannabinoid, CBD can improve cognition and deficits in social interaction in a maternal immune activation (MIA) model relevant to the etiology of schizophrenia. Although, the mechanisms that are basic to this effect remain unknown.

An imbalance within the primary excitatory (glutamate) and inhibitory (GABA) neurotransmitter processes inside the brain plays an integral part in the pathophysiology of schizophrenia.

For this reason, the endocannabinoid system can act as a therapeutic target for schizophrenia as a controller of glutamate and GABA release through the CB1 receptor (CB1R).

To carry out the investigation time mated pregnant Sprague-Dawley rats were administered intravenously poly I:C (4mg/kg) or saline on gestational day. CBD was injected to the male offspring (10mg/kg. i.p) or vehicle twice daily from postnatal day 56 for 3 weeks. The prefrontal cortex (PFC) and hippocampus (HPC) were collected for post-mortem receptor binding and Western blot analyses which is generally applied in research to separate and identify proteins. CBD treatment decreased poly I:C -induced deficits in cannabinoid CB1 receptor binding in the prefrontal cortex and glutamate decarboxylase 67, the enzyme that converts glutamate to GABA, in the hippocampus.

CBD therapy raised parvalbumin levels inside the hippocampus irrespective of whether offspring were exposed to poly I:C in utero. On the contrary, CBD did not affect N-methyl-d-aspartate receptor and gamma-aminobutyric acid (GABA) A receptor binding or protein levels of fatty acid amide hydrolase (FAAH), the enzyme that breaks down the endocannabinoid anandamide. On the whole, these findings reveal that CBD can revive cannabinoid/GABAergic signaling deficits in areas of the brain implicated in schizophrenia pathophysiology subsequent to maternal poly I:C exposure. These findings offer new evidence for the possible mechanisms underlying the therapeutic impact of CBD treatment in the poly I:C model.

CBD Also Works As An Allosteric Modulator

CBD can perform as an allosteric receptor modulator, meaning that it can enhance or curb the way in which a receptor sends a signal by altering the shape of the receptor. CBD communicates with the GABA-A receptor in a manner that promotes the receptor’s binding affinity for its primary endogenous agonist, GABA which is the chief inhibitory neurotransmitter in the central nervous system.

The tranquillizing effects of Valium and various Benzos are controlled by GABA receptor transmission. CBD lowers anxiety by altering the shape of the GABA-A receptor in a manner that boosts the natural calming influence of GABA. The brain circuits within the amygdala are found to contain inhibitory networks of GABAergic interneurons which is a neurotransmitter that plays a primary part in the modulation of anxiety reactions in the normal and pathological state.

Exclusive Effects Of CBD

Most cannabinoids can attach to both CB1 and CB2 receptors. This is precisely for both the endocannabinoids – anandamide and 2-AG – and also for plant cannabinoids such as THC. However, the plant compound CBD does not directly activate either receptor. Rather, it alters the receptor’s ability to attach to cannabinoids.

In addition, CBD performs extensively on the endocannabinoid system and influences various receptors, while also boosting the natural levels of endocannabinoids by involving different enzymes.

Further, CBD displays positive influence in situations where glutamatergic signaling, specifically that mediated by N-methyl-D-aspartate acid receptor (NMDAR) has a decisive role. Accordingly, CBD displays antioxidant properties and safeguards neurons from glutamate-induced death but devoid of any cannabinoid receptor activation or NMDAR antagonism.


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