How CBD Operates


Learn how CBD interacts with the endocannabinoid system in your body.

How CBD Operates? Cannabidiol (CBD), a non-psychoactive component of the cannabis plant, has aroused substantial interest among scientists and physicians in recent years; however, the molecular mechanisms by which CBD exerts its medicinal effects are still being elucidated. Cannabidiol is a pleiotropic medication, meaning it exerts numerous effects via multiple biochemical mechanisms. In the scientific literature, more than 65 molecular targets of CBD have been identified.

Cannabidiol affects a number of non-cannabinoid receptors and ion channels, despite its low affinity for the two cannabinoid receptors CB1 and CB2. CBD also operates via other receptor-independent routes, such as by delaying the “reuptake” of endogenous neurotransmitters (such as anandamide and adenosine) and by boosting or inhibiting the binding action of specific G-protein coupled receptors.

Here are a few of the numerous therapeutic effects of CBD.

How CBD Operates: Serotonin Receptors

The pioneering research on CBD and the neurological correlates of anxiety was undertaken by Jose Alexandre Crippa and his colleagues at the University of So Paulo in Brazil and King’s College in London. CBD directly stimulates the 5-HT1A (hydroxytryptamine) serotonin receptor at high dosages, producing an anti-anxiety action. This G-coupled protein receptor is involved in a variety of biological and neurological processes, including anxiety, addiction, appetite, sleep, pain perception, nausea, and vomiting.

5-HT1A belongs to the 5-HT receptor family, which is activated by the neurotransmitter serotonin. Depending on the chemical context of the message, 5-HT receptors found in both the central and peripheral nervous systems initiate numerous intracellular cascades of chemical messengers that create either an excitatory or inhibitory response.

CBDA [Cannabidiolic acid], the unheated, unprocessed form of CBD found in cannabis, has a significant affinity for the 5-HT1A receptor (even more so than CBD). CBDA is a more potent antiemetic than either CBD or THC, which also have anti-nausea characteristics, according to preclinical research.

Vanilloid Receptors

CBD interacts directly with many ion channels to have a medicinal effect. CBD binds to TRPV1 receptors, which are also ion channels. Pain perception, inflammation, and body temperature are all known to be mediated by TRPV1.

The acronym TRPV refers to “transient receptor potential cation channel subfamily V.” TRPV1 is one of dozens of TRP (pronounced “trip”) receptor variations or subfamilies that mediate the effects of numerous therapeutic plants.

TRPV1 is also known as a “vanilloid receptor,” a term derived from the tasty vanilla bean. Vanilla contains eugenol, an essential oil with antibacterial, analgesic, and blood vessel-dilating effects. Historically, vanilla beans were employed as a folk remedy for headaches.

CBD binds to TRPV1, which can alter the experience of pain.

The capsaicin found in hot chili peppers stimulates the TRPV1 receptor. The endogenous cannabinoid anandamide is also a TRPV1 agonist.

How CBD Operates: GPR55—Orphan Receptors

In contrast to the direct activation of the 5-HT1A serotonin receptor and many TRPV ion channels by cannabidiol, other research suggest that CBD acts as an antagonist that inhibits or deactivates the GPR55 G protein-coupled receptor.

GPR55 has been nicknamed a “orphan receptor” since scientists are unsure whether it belongs to a wider receptor family. GPR55 is abundantly expressed in the brain, particularly the cerebellum. In addition to other physiological functions, it modulates blood pressure and bone density.

GPR55 stimulates osteoclast cell activity, hence promoting bone reabsorption. Osteoporosis is connected with GPR55 receptor signaling that is too active.

According to a study published in 2010 by the Chinese Academy of Sciences in Shanghai, GPR55 activation also stimulates the multiplication of cancer cells. This receptor is expressed in numerous cancer types.

Ruth Ross of the University of Aberdeen announced at the 2010 conference of the International Cannabinoid Research Society in Lund, Sweden, that CBD is a GPR55 antagonist. By inhibiting GPR55 signaling, CBD may reduce both bone reabsorption and the growth of cancer cells.

How CBD Operates: PPARS – Nuclear Receptors

CBD also exerts an anticancer impact via activating PPARs (peroxisome proliferator-activated receptors) located on the cell nucleus’s surface. In human lung cancer cell lines, activation of the receptor known as PPAR-gamma has an anti-proliferative effect and the capacity to cause tumor regression. Activation of PPAR-gamma destroys amyloid-beta plaque, a crucial chemical associated with the onset of Alzheimer’s disease. This is one of the reasons why PPAR-gamma agonist cannabidiol may be an effective treatment for Alzheimer’s sufferers.

Genes involved in energy homeostasis, lipid uptake, insulin sensitivity, and other metabolic activities are also regulated by PPAR receptors. Consequently, diabetics may benefit from a therapy plan rich in CBD.

How can CBD, an external plant chemical, enter human cells in order to connect to nuclear receptors? It must first pass through the cell membrane by hitching a ride with a fatty acid binding protein (FABP), which chaperones different lipid molecules into the cytoplasm. These intracellular transport molecules also transport tetrahydrocannabinol (THC) and the brain’s own cannabis-like chemicals, the endocannabinoids anandamide and 2AG, over the cell membrane to their respective intracellular destinations. CBD and THC both alter nucleus-surface receptors that control gene expression and mitochondrial function.

It turns out that cannabidiol has a great affinity for three types of FABPs, and it competes with our endocannabinoids, which are fatty acids, for the same transport molecules. FAAH [fatty acid amide hydrolase], a metabolic enzyme, breaks down anandamide within the cell as part of its natural molecular life cycle. CBD hinders this process by limiting anandamide’s access to FABP transport molecules and delaying endocannabinoid entry into the cell’s interior.

According to a group of experts from Stony Brook University, CBD acts as an anandamide reuptake and breakdown inhibitor, hence increasing endocannabinoid levels in the synapses of the brain. Enhancing endocannabinoid tone by inhibiting reuptake may be a fundamental mechanism by which CBD delivers neuroprotective effects against seizures and numerous other health benefits.

CBD’s anti-inflammatory and anti-anxiety properties are related, in part, to its ability to prevent adenosine reuptake. CBD increases adenosine levels in the brain by delaying the reuptake of this neurotransmitter, hence regulating adenosine receptor activation. A1A and A2A adenosine receptors regulate myocardial oxygen consumption and coronary blood flow, playing crucial functions in cardiovascular function. These receptors exert systemic anti-inflammatory actions.

CBD an an allosteric modulator

CBD also operates as an allosteric receptor modulator, meaning that it can boost or inhibit the signal transmission of a receptor by altering the receptor’s structure.

According to Australian researchers, CBD functions as a “positive allosteric modulator” of the GABA-A receptor. In other words, CBD interacts with the GABA-A receptor in a manner that increases the receptor’s binding affinity for its primary endogenous agonist, gamma-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the human central nervous system. GABA receptor transmission mediates the tranquilizing effects of Valium and other Benzos. CBD decreases anxiety by altering the geometry of GABA-A receptors in a way that enhances GABA’s inherent calming impact.

Scientists from Canada have identified CBD as a “negative allosteric modulator” of the brain and central nervous system-concentrated cannabinoid CB1 receptor. CBD interacts allosterically with CB1 and alters the receptor’s structure in a way that reduces the receptor’s affinity for THC.

As a negative allosteric modulator of the CB1 receptor, CBD reduces the psychoactivity of THC, which explains why people feel less “high” while consuming CBD-rich cannabis compared to when they consume THC-dominant treatment. A CBD-rich product with low THC content can provide medicinal benefits without producing euphoria or dysphoria.

Cannabinoids Garden