The most relevant receptors and ion channel targets of CBD.

This is going to get a little nerdy. You will have to look up words like I did to understand this lol. If you are not interested in how CBD works, This post is not for you lol.

CB1 and CB2:

CBD acts as a negative allosteric modulator of the CB1 receptor. This means that CBD doesn’t directly compete with agonist compounds like anandamide and THC at their binding site of CB1. Instead, CBD interacts with a different part of the receptor, effectively decreasing the receptor’s activity level when stimulated by the agonists. CBD doesn’t inhibit the receptors, like rimonabant and other antagonists, but limits the intensity of the receptors’ response to agonists. Think of CBD as turning down the volume of the CB1 receptor's signal, but not shutting it off. 

Some data indicates CBD may have a similar effect as a negative allosteric modulator on the CB2 receptor, though this has not been proven.

Serotonin Receptors:

CBD stimulates the serotonin 5-HT1A receptor , possibly a common tool for reducing anxiety, reducing the damage of brain ischemia (stroke), reducing nausea, and improving cognition in hepatic encephalopathy . The 5-HT1A receptor is the most widespread serotonin receptor in the central nervous system and is involved in the activity of several anti-anxiety and antidepressant medications. 5-HT1A activation is also associated with improved cognition, decreased aggression, increased sociability, decreased impulsivity, inhibition of drug-seeking behavior, and facilitation of sex drive and arousal.(woohoo)!

Adenosine Receptors:

Adenosine receptors have several functions in the body including regulation of heart function, inflammation, and dopamine and glutamate release in the brain. The adenosine receptor is well-known as a target of caffeine, which inhibits the A1 and A2 receptors and provides a stimulating effect. Studies have shown that CBD likely stimulates the adenosine A1 receptor, perhaps indirectly by preventing the intake of adenosine. This mechanism has been shown to prevent irregular heart rhythm in a rodent model of heart attack. CBD also likely stimulates the Adenosine A2 receptor, leading to anti-inflammatory and possibly neuroprotective effects.

Stimulating these receptors would typically provide a sedating effect, so this is likely not the mechanism by which CBD increases alertness. The alerting effects are more likely due to serotonin receptor activation.

Glycine Receptors:

Glycine receptors mediate neuropathic pain and inflammation. CBD and its analogue dehydroxyl-CBD have been shown to suppress neuropathic pain in rats with spinal nerve injury by targeting the α3 glycine receptor.

GPR55:

GPR55 is a membrane receptor activated by endocannabinoids, phytocannabinoids, and synthetic cannabinoids. CBD antagonizes GPR55, resulting in anti-inflammatory effects and decreased migration of immune cells called neutrophils.

Ion Channels:

Transient receptor potential (TRP) channels are present in the membrane of a variety of cells in many tissues. They act as nonselective channels that absorbs sodium, calcium, and magnesium ions, and are opened by a ligand. The TRPV1 channel is also known as the “capsaicin receptor,” based on the ability for an active component of hot peppers to bind and stimulate it. CBD is also an agonist at TRPV1, likely a mechanism of pain-relief and anti-inflammatory effects, and potentially one mechanism of the anti-psychotic effects. Unlike capsaicin, which is commonly used in topical preparations for arthritis, CBD does not cause a burning sensation in the mouth or on the skin.

Evidence also suggests CBD stimulates several other TRP channels with unknown significance.

VDAC1, known as mitochondrial porin, is an ion channel most often located on the outer membrane of mitochondria, the energy production organelle of the cell, although has also been reported to be present on cell plasma membranes as well. VDAC1 plays a complex and important role in a variety of cell functions such as cellular energy rationing, calcium homeostasis, apoptosis (programmed cell death), and protection against oxidative stress. CBD’s activity on VDAC1 and mitochondrial calcium likely provides some of its neuroprotective effects.

Thank you readers for your interest in the article. Please like and comment so we have more motivation to write articles