A study published in 2008 indicated that CBD injections into the dorsolateral periaqueductal gray area of rats reduced anxiety via 5-HT1A receptor interaction.  Researchers noted that the 5-HT1A receptors were more involved than cannabinoid receptors (e.g. CB1) in reducing anxiety.  The study concluded that cannabidiol interacts directly with 5-HT1A receptors to yield an anxiolytic response.

In early June, I met with Penny Pennington Howard, a mother of three, who lives in Carrollton, Texas, about 25 minutes outside of Dallas. Posted in the glass of her front door are two signs you can’t quite make out from the sidewalk: one asking visitors not to smoke, as oxygen treatments are in use; the other a yellow diamond informing guests this is the home of a special needs child. Penny welcomed me inside, out of the glare of the sun, and led me through her living room into her kitchen, where her kids were gathered for lunch. Seth, then eight months old, was plucking cereal off the tray of his highchair, while Lily, seven, was darting back and forth between the countertop and table. Harper, a blond five-year-old with hot pink toenails, was reclining in her “tomato chair,” a molded plastic seat with straps to help keep her steady.


When Meagan’s in-laws suggested they look into medical marijuana, she recoiled. “This is a federally illegal drug we are talking about,” she recalls thinking. But she did her own research. A good deal of anecdotal evidence shows that high-CBD strains of cannabis can have a strong antiseizure effect. The medical literature, though scant, goes back surprisingly far. In 1843 a British doctor named William O’Shaughnessy published an article detailing how cannabis oil had arrested an infant’s relentless convulsions.
Relevant studies are summarized in Table ​Table3.3. In a SPECT study of resting cerebral blood flow (rCBF) in normal subjects, CBD reduced rCBF in left medial temporal areas, including the amygdala and hippocampus, as well as the hypothalamus and left posterior cingulate gyrus, but increased rCBF in the left parahippocampal gyrus. These rCBF changes were not correlated with anxiolytic effects [102]. In a SPECT study, by the same authors, in patients with SAD, CBD reduced rCBF in overlapping, but distinct, limbic and paralimbic areas; again, with no correlations to anxiolytic effects [104].

A bit of online digging led me to realize that the active ingredient in Charlotte's Web Everyday Plus Hemp Oil, the product I'd been offered to test, was the chemical compound CBD, which stands for Cannabidiol. Unlike THC, the other crucial compound in hemp and marijuana plants, CBD does not produce the psychoactive effects that make you feel "high"; instead, it actually eases anxiety and makes you less likely to freak out.


No medication seemed to provide a great deal of relief for Harper’s symptoms. But in 2013, three years after their trip to Boston, Penny and Dustin caught an installment of CNN’s medical marijuana documentary and began researching what they could obtain in Texas, where medical marijuana is illegal. Their internet searches soon led them to HempMedsPx and Real Scientific Hemp Oil. The company sent Penny a vial of hemp oil, which she administered to Harper that September.
It also is distinct from THC which acts as a CB1/CB2 partial agonist, thereby stimulating the receptor sites.  If it acted the same as THC at the CB1/CB2 receptor sites, its therapeutic potential may be reduced.  Moreover, since cannabidiol acts as an inverse agonist at the CB1/CB2 receptor sites, it doesn’t induce psychological euphoria and/or pleasure associated with downstream dopaminergic enhancement in the mesolimbic pathway (resulting from CB1/CB2 agonism).

A review published in 2017 in the journal Frontiers in Pharmacology described how CBD may work to protect the hippocampus — the part of the brain responsible for several important functions, such as learning, memory and navigation — during times of stress, and may also help prevent brain-cell destruction that results from schizophrenia. Another 2017 review published in the journal Annals of Palliative Medicine summarized a handful of studies that suggest cannabis oils containing THC or CBD, or both, may help with chronic pain management, but the mechanism is unclear.

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