Scientists have made a lot of progress in understanding how CBD produces its calming, pain-reducing, anti-inflammatory effects in the body—and there’s still more to learn. We know that CBD interacts with many different receptors, proteins, and other chemicals in the brain. These interactions create changes in the activity of neurotransmitters, hormones, and other cells throughout the brain and body. Through these interactions, CBD appears to be able to affect many of the body’s functions, from sleep-wake cycles and emotional regulation to inflammation, pain perception, and seizures.
My grandson has severe anxiety. His anxiety and meltdowns were so severe that we couldn’t go shopping, out to eat, or anything else normal people do. The medicines his doctors put him on have horrible side effects. We started him on the cbd oil once a day. Within a couple weeks we saw a huge difference. Yes, he still has some anxiety, and meltdowns, but nothing like they were. We can actually go you the grocery store with him now! And it’s not a coincidence because when we run out for a few days we can see the difference! – Dian
The 5-HT1A receptor (5-HT1AR) is an established anxiolytic target. Buspirone and other 5-HT1AR agonists are approved for the treatment of GAD, with fair response rates [50]. In preclinical studies, 5-HT1AR agonists are anxiolytic in animal models of general anxiety [51], prevent the adverse effects of stress [52], and enhance fear extinction [53]. Both pre- and postsynaptic 5-HT1ARs are coupled to various members of the Gi/o protein family. They are expressed on serotonergic neurons in the raphe, where they exert autoinhibitory function, and various other brain areas involved in fear and anxiety [54, 55]. Mechanisms underlying the anxiolytic effects of 5-HT1AR activation are complex, varying between both brain region, and pre- versus postsynaptic locus, and are not fully established [56]. While in vitro studies suggest CBD acts as a direct 5-HT1AR agonist [57], in vivo studies are more consistent with CBD acting as an allosteric modulator, or facilitator of 5-HT1A signaling [58].

PPAR agonism: Agonism of PPARs (peroxisome proliferator activated receptors) may have a variety of benefits including: anticancer, neuroprotective (via removal of beta-amyloid plaques), and antipsychotic effects.  Cannabidiol bolsters PPAR-alpha signaling and simultaneously decreases inflammation.  Although PPAR agonism may not directly foster an anxiolytic effect, it cannot be ruled out as a potential synergistic contributor.


Grant says this may lead to a “dampening” or mellowing of some neurochemical processes, including those linked to pain. “CBD may also react with other receptors, like those for serotonin, and it may have actions that reduce the inflammatory molecules produced whenever there is tissue damage or bacteria coming in,” he says. “But we really don’t know the mechanisms.”
Cannabidiol has been found to act as an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain.[33] It has also been found to act as an inverse agonist of GPR3, GPR6, and GPR12.[14] Although currently classified as orphan receptors, these receptors are most closely related phylogeneticaly to the cannabinoid receptors.[14] In addition to orphan receptors, CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist,[34] and this action may be involved in its antidepressant,[35][36] anxiolytic,[36][37] and neuroprotective effects.[38][39] It is an allosteric modulator of the μ- and δ-opioid receptors as well.[40] The pharmacological effects of CBD have additionally been attributed to PPARγ agonism and intracellular calcium release.[8]
CBD is short for cannabidiol, a cannabinoid compound that is found in hemp and marijuana. Both hemp and marijuana are part of the plant family known as Cannabis. The main difference between marijuana and hemp is the level of THC in each. THC, like CBD, is a cannabinoid compound. There are 60 different known cannabinoids, but THC is the most well-known—the Beyoncé of cannabinoids, if you will. The reason THC is so famous is because it's associated with the psychoactive high that people experience after smoking or ingesting weed.
Support for legalization has steadily grown over the last several years. Today, medical marijuana is legal in 23 states and the District of Columbia. And even federal officials have begun to soften their stances. Last fall, outgoing Attorney General Eric Holder signaled his support for removing marijuana from the list of Schedule I narcotics. “I think it’s certainly a question we need to ask ourselves, whether or not marijuana is as serious of a drug as heroin,” Holder said. This summer, Chuck Rosenberg, the acting administrator of the U.S. Drug Enforcement Administration, acknowledged that marijuana is not as dangerous as other Schedule I drugs and announced his agents would not be prioritizing marijuana enforcement. Still, as long as marijuana remains illegal under federal law, the haphazard system in which it is studied, produced, and distributed will remain, and Americans will not be able to take full advantage of its medicinal properties.

As Kane leads me around his lab, I see the excitement on his face and on the faces of his young staff. The place feels almost like a start-up company. “So much of science is incremental,” he says, “but with this cannabis work, the science will not be incremental. It will be transformative. Transformative not just in our understanding of the plant but also of ourselves—our brains, our neurology, our psychology. Transformative in terms of the biochemistry of its compounds. Transformative in terms of its impact across several different industries, including medicine, agriculture, and biofuels. It may even transform part of our diet—hemp seed is known to be a ready source of a very healthy, protein-rich oil.”

However, Bonn-Miller told Live Science that he thinks cannabis research is on the upswing. "If we flash forward five years I think you'll see more studies," he said. Those studies could reveal more conditions that CBD may be helpful for and may also reveal that some of the reasons why people say they use CBD oil are not supported by the science but are instead a placebo effect. "And that's why we need to do the studies," he said.  

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