Effects of CBD on Important Receptors
Published 28 Oct 2020

Cannabidiol, or CBD, is a non-psychoactive cannabinoid in cannabis plants. It generates enormous interest among everyone worldwide, from scientists and doctors to patients and generally health conscious folks. How it works is still under study, however. It is pleiotropic. It exerts its many therapeutic effects in a variety of ways, using different mechanisms of action and different molecular pathways.

Evidence finds over 65 molecular targets of CBD already. Is CBD safe? Although it has little desire to bind to the cannabinoid receptors CB1 and CB2, it modulates several ion channels and non-cannabinoid receptors. It also acts through receptor-independent pathways by, for example, delaying reuptake of endogenous neurotransmitters. It also boosts or inhibits binding of G-protein coupled receptors.

Serotonin Receptors

Pioneering research into CBD and neural correlates of anxiety makes for interesting reading. According to the U.S. National Library of Medicine, at high concentrations, CBD oil products activate the 5-hydroxytryptamine, or 5-HT1A, serotonin receptor. This confers an immediate anxiolytic effect. It also affects an array of processes, from addiction to sleep, appetite, nausea, pain perception, and more.

A member of the 5-HT receptor family, 5-HT1A needs the neurotransmitter serotonin to execute its duties. Found in both the peripheral and central nervous systems, the 5-HT family triggers different intracellular messages to either excite or inhibit a response, depending on the message and its exact chemical context. Cannabidiolic acid, or CBDA, CBD’s precursor, also triggers 5-HT1A, more than CBD.

Vanilloid Receptors

CBD interacts directly with specific ion channels to exert a medicinal effect. For example, it binds to TRPV1 receptors, also functioning ion channels. TRPV1 famously mediates inflammation, pain perception, and body temperature. It is one of several belonging to the transient receptor potential V family, or TRPV, the variants and subfamilies which mediate effects of a wide array of therapeutic herbs.

To scientists, TRPV1 is a vanilloid receptor, named so after vanilla beans, which contain eugenol. Eugenol has both analgesic and antiseptic properties. It unclogs blood vessels too, and historically, vanilla beans were popular treatments for headaches. CBD binds to TRPV1, influencing pain perception. Other TRPV1 agonists include the cannabinoid anandamide and capsaicin, a chemical in chili peppers.

Orphan Receptors – GPR55

While CBD oil products activate some receptors, like 5-HT1A, and a few TRPV ion channels, it also acts as an antagonist to deactivate, or block, GPR55, another G-protein-coupled receptor. Called an “orphan receptor,” scientists are unsure of its exact family. No idea where to place it. It expresses widely in the brain, particularly the cerebellum. It modulates bone density, blood pressure, and other body functions.

GPR55 facilitates reabsorption of bone. It does so by promoting osteoclast cell function. Too much signaling by this receptor associates with osteoporosis. According to a study in Nature, GPR55 proliferates cancer cells. It expresses in various cancers. CBD is an antagonist of GPR55. It effectively blocks signaling by this receptor and slows both cancer cell proliferation and bone reabsorption.

Nuclear Receptors – PPARS

By activating peroxisome proliferator activated receptors, or just PPARs, CBD proves its anticancer properties. These receptors live on the surface of cell nuclei. Activating PPAR-gamma has specific anti-proliferative effects, as well as a proven ability to regress tumors in cancerous lung tissue. It also degrades amyloid-beta, a plaque linked to the onset of debilitating Alzheimer’s disease.

For this reason, much speculation exists as to the usefulness of CBD in treating Alzheimer’s patients. As a PPAR-gamma agonist, CBD might prove especially helpful. These receptors also regulate the genes responsible for maintaining energy homeostasis, as well as sensitivity to insulin, lipid uptake, and other metabolic processes. As such, diabetics, in particular, might benefit from CBD therapy.

Reuptake Inhibition

Your body needs to absorb CBD for it to bind to nuclear receptors. This involves attaching to fatty acid binding proteins, or FABP, in order to pass through cell membranes. FABP transport lipid compounds into cells. They also chaperone tetrahydrocannabinol, or THC, as well as endocannabinoids 2AG and anandamide, across several targets inside cells.

Both THC and CBD modulate receptors on surface of nuclei, which regulate mitochondrial action and gene expression. CBD finds three FABPs especially attractive, competing with endocannabinoids, themselves fatty acids, for a lucrative spot on traveling FABPs. When in cells, fatty acid amide hydrolase, or FAAH, a metabolic enzyme, breaks anandamide down as part of its natural life cycle.

However, CBD disrupts this process. It prevents access of anandamide to FABP transport molecules, thereby delaying its passage into a cell’s interior. According to the U.S. National Library of Medicine, CBD acts as both a breakdown and reuptake inhibitor of anandamide, raising levels of endocannabinoids within synapses of the brain. In this way, CBD confers neuroprotective effects and other benefits.

What is more, the anxiolytic and anti-inflammatory effects of CBD are partly due to its inhibition of adenosine reuptake. CBD raises adenosine levels by delaying this neurotransmitter’s reuptake, which regulates activity of receptors. Anti-inflammatory A1A and A2A adenosine receptors are crucial to cardiovascular health, regulating consumption of both coronary blood flow and myocardial oxygen.

Allosteric Modulation

By inhibiting or enhancing how receptors transmit, usually by changing receptor shape, CBD modulates allosteric receptors. The U.S. National Library of Medicine proves CBD a positive allosteric modulator of GABA-A receptors. It boosts binding affinity for prime endogenous agonists, being the main inhibitory neurotransmitter in central nervous systems of mammals, gamma-Aminobutyric acid, or GABA.

GABA receptor transmission is what mediates the effects of sedatives, such as Valium. CBD works by using another mechanism of action to reduce anxiety. It changes GABA-A receptor shape in a manner that amplifies the calm of GABA. CBD is also a negative allosteric modulator, specifically of the CB1 endocannabinoid receptor, which concentrates in the central nervous system, particularly the brain.

While CBD does not bind to CB1 receptors the direct way that THC does, it interacts instead allosterically with it to change its shape in a way that weakens its ability to ever bind with THC. This is important, as in this way, CBD reduces the psychoactivity of THC, essentially rendering it less effective. This is why folks do not feel “high” after consuming large doses of CBD.

Buy Hemp Oil Online

CBD is widely available. You can find CBD oil products galore online. From CBD capsules to edibles for pain, there is something for everyone. However, before diving into CBD use, whether therapeutically or preventively, it is important to understand which receptors it affects, and how it affects them. Although CBD cannot make you stoned, it does have effects worth knowing and understanding beforehand.


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