CBD and brain activity: An overview

by Duncan Fisher

November 01, 2022 - 3 min read

Evidence is abundant now that cannabidiol (CBD), while non-intoxicating, has effects on the brain, notably as an antipsychotic and an anxiolytic. The neurobiological substrates underlying these are beginning to be elucidated.In healthy volunteers and individuals with psychiatric disorders CBD appears to modulate cognitive activity in ways generally opposite to the effects of THC. Research studies are clarifying the specifics. 

Acute administration of CBD has been shown to enhance fronto-striatal connectivity after CBD administration during resting state, and to enhance activity during salience processing. This could be useful in therapeutics, as lower functional connectivity in the fronto-striatal networks is described in psychosis. CBD also decreases fronto-limbic activity during resting state, and emotional processing as well. This too is useful, because functional fMRI studies show that limbic areas activate in panic disorders. Finally, in substance use disorders, CBD seems to help in reducing craving, negative affect, and motivation, all of which are associated with fronto-striatal and limbic network imbalances.

THC has pro-psychotic and anxiogenic properties, particularly at high doses, and dampening effects in cognitive processing. Striatum activity correlates with psychotic symptoms after THC, and diverging amygdala activity correlates with anxiety after CBD and THC together. CBD may thus counterbalance the effects of THC. 

In psychotic individuals, CBD has shown moderate activity compared with patients receiving placebo and healthy subjects, in brain regions involved in reward and salience processing. The same is true during memory tasks. Here too, then, CBD might be able to normalize imbalanced fronto-striatal activity in patients with psychosis. Cerebral blood flow as well, in the hippocampus and parahippocampal and inferior temporal gyrus, is reported in subjects with social anxiety, which dovetails with decreased fronto-limbic activity in healthy individuals reported after CBD, and suggests that the anxiolytic effect of CBD may be a function of its ability to modify brain activity in limbic and paralimbic areas. In autism, as well, spectroscopic study has shown similar glutamate changes to healthy controls (both increased in basal ganglia, and decreased in prefrontal cortex) and opposite GABA (decreased in patients, increased in controls) after CBD administration. This has been observed even with single dosing. 

CBD may directly inhibit the reuptake of anandamide, an endocannabinoid, elevation of which has been shown to associate with antipsychotic effects. Endocannabinoids are retrograde messengers, so it may be that downstream release of GABA and glutamate is attenuated, and dopamine levels are stabilized. Most of the reported effects of CBD occur in brain areas rich in CB1 receptors. CB1 receptors downregulate in chronic cannabis users. It may be that CBD’s antagonistic effects could modulate these receptors by binding to some distinct allosteric site. Or it may simply prevent down-regulation of CB1 receptors. Other possible mechanisms of action of CBD are its agonist activity on 5HT1A receptors, partial agonist activity on dopamine D2 receptors, or activation of vanilloid receptor 1, a non-selective calcium channel, which could itself enhance glutamate release. 


DiolPure products contain PureForm CBD™ transformed from aromatic terpenes for pharmaceutical-grade purity. PureForm CBD™ is bioidentical to CBD extracted from hemp and cannabis, but free of any residual cannabinoids like THC or impurities or chemicals that can associate with traditional plant-derived production processes. 

The foregoing is a report on trends and developments in cannabinoid industry research. No product description herein is intended as a recommendation for diagnosis, treatment, cure or prevention of any disease or syndrome. 

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