In addition to CBD's indirect activation of the endocannabinoid Anandamide, CBD also functions in other ways at the molecular level to act therapeutically in humans. To reiterate, CBD does not bind to either of the two cannabinoid receptors, though it has been shown to directly interact with other “G-protein-coupled” receptors and "ion channels" (i.e., a class of proteins) to provide therapeutic effects.
For example, CBD binds to the TRPV-1 receptor (aka. the Vanilloid or Capsaicin receptor), which is known to regulate pain, inflammation and body temperature. CBD is an “agonist” of TRPV-1, which stimulates the receptor. This is likely one of the reasons why CBD-rich cannabis is an effective treatment for neuropathic pain.
At high concentrations, CBD is also an agonist of the 5-HT1A (hydroxytryptamine) serotonin receptor. This receptor is found in the central and peripheral nervous systems and is involved in regulating anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting. CBD triggers a response that slows down 5-HT1A signaling, causing an antidepressant affect.
CBD also activates our Adenosine receptors, which play a role in cardiovascular and coronary functions and provides anti-inflammatory effects throughout the body.
In contrast to its functions as an agonist, some studies have also shown that CBD can act as an antagonist that blocks, or deactivates, another G protein-coupled receptor known as GPR55. GPR55 is found in the brain, especially in the cerebellum. According to the CBD Project, "GPR55 is involved in modulating blood pressure and bone density, among other physiological processes. GPR55 promotes osteoclast cell function, which facilitates bone re-absorption. Overactive GPR55 receptor signaling is associated with osteoporosis...when activated, GPR55 also promotes cancer cell proliferation..." Because CBD blocks GPR55 signaling, it may help to decrease bone re-absorption and cancer cell proliferation.
Lastly, CBD may act as an agonist to activate the Peroxisome Proliferator-Activated Receptors (PPARs). PPARs regulate genes that are involved in energy homeostasis, lipid uptake, insulin sensitivity, and other metabolic functions. And activation of a certain type of PPAR-gamma activation degrades amyloid-beta plaque, a key molecule linked to the development of Alzheimer’s disease. The ability of CBD to activate various types of PPARs provide possible anti-cancer effects, decrease schizophrenic symptoms and may someday aid in a treatment for Alzheimer's.
How Does CBD Work?
The medical community is just starting to recognize the medical potential of CBD. Here is a partial list of the therapeutic applications of CBD.
-may help in the treatment of epilepsy. Project CBD.org offers an entire page devoted to studies on CBD and Epilepsy.
-may help with muscle spasticity. Study 1.
-may help to reduce schizophrenia symptoms. Study 1.
-may help with heart & circulation. Study 1.
-may help in treating neuropathy from chemo drugs. Study 1.
-may help in addressing diseases with demyelination like MS. Study 1.
-may help in treating disc degeneration. Study 1.
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Possible Therapeutic Effects
What is CBD?
In 2013 Cannabidiol, or CBD, became a topic of discussion in the U.S. after a young girl named Charlotte Figi was profiled on a CNN documentary about cannabis. She was using a high CBD/low THC strain bred by the Stanley Brothers out of Colorado to successfully reduce her epileptic seizures brought on by Dravet Syndrome. Charlotte's story spawned a social movement of sorts wherein many parents with epileptic children wanted to explore if CBD could help their kids, too. The medical value of Cannabidiol (CBD) is just starting to be explored by scientists. CBD shows promise as an anti-inflammatory, antioxidant, neuroprotectant, anxiolytic, antidepressant, analgesic, anti-tumoral agent and an anti-psychotic. But what exactly is CBD and how can it potentially work to help humans therapeutically?
Unlike THC, CBD does not bind to the CB1-R or CB2-R cannabinoid receptors. Instead, CBD indirectly activates the human body's own 'endogenous' cannabinoid signaling by suppressing the enzyme Fatty Acid Amide Hydroxylase (FAAH). This FAAH enzyme degrades Anandamide, which is an important endocannabinoid that exists naturally in the human body. As illustrated in the graphic below, CBD's indirect suppression of FAAH significantly slows down the degradation of Anadamide, which allows for greater, more prolonged CB1-R receptor activation.
Cannabidiol is one of the most prevalent non-psychoactive cannabinoid compounds in the cannabis plant. CBD can be described as "pleiotropic", which simply means that it produces multiple effects through many molecular pathways. How CBD functions therapeutically at the molecular level is a mystery that scientists are working on and will continue to uncover for years to come.
At the molecular level, CBD is ultimately formed when its precursor acid form, CBDa, is converted to its neutral form - CBD. CBDa is one of the three major cannabinoid branches formed by Cannabigerolic Acid (CBGa). The cannabis plant possesses natural enzymes, referred to as "synthases", that break the CBGa down and convert it to one of the major cannabinoids. As shown in the graphic below, you can see at a high level the tranformation from CBGa to CBDa and then finally forming CBD with the loss of a CO2 molecule via decarboxylation.
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