If you aren’t very familiar with it, you’ve probably at least heard of CBD. Otherwise known as cannabidiol, it is one of the chemical compounds of the cannabis plant. In the health and wellness community, people appreciate CBD for its non-psychoactive properties and its potential benefits for therapeutic use. Many users of CBD claim that it has helped them find relief from pain, inflammation, anxiety and other symptoms.
A lesser known topic about CBD is the impact it can have at the molecular level. At this time, scientists have been able to identify 65 different molecules that can be affected by CBD. When it binds to cannabinoid receptors, the ensuing reaction, or binding affinity, is weak. CB1 receptors are found in the nervous system, whereas some of the body’s peripheral tissues also contain CB1 as well as CB2 receptors. Their role is to ensure a healthy, proper function of the brain. How, then, does CBD work? It regulates other receptors and ion pathways. For instance, it can slow down neurotransmitters, which send signals from one neuron, cell, or gland to another.
CBD can also augment or interfere with membrane receptors such as G-protein-coupled receptors. These are proteins in cell membranes that bind substances together while transmitting signals from them. In simpler terms, they play a role in the body’s physiological response to various elements. One of the chief neurotransmitters of the human brain is GABA, or gamma aminobutyric acid. In this post, we’ll discuss how CBD affects GABA to better understand some of the primary benefits that researchers are exploring. In order to completely grasp the link between GABA and CBD, however, you first need to understand how CBD interacts with other receptors in the nervous system.
Serotonin is produced by nerve cells. The chemical comes from tryptophan, one of the essential amino acids. It sends signals from one cell to another. Where can serotonin be found? It is mainly located in the digestive and central nervous systems as well as blood platelets.
Someone with a deficiency of it may be more likely to experience depression, anxiety, and other mood disorders. That’s because the role of serotonin is to help manage motor skills as well as stabilize one’s emotions.
When serotonin acts as a neurotransmitter, it activates the body’s serotonin receptors, which can affect anything from mood and appetite to cognition and sleep. Cannabidiol may be capable of activating a serotonin receptor called 5-HT1A, which is responsible for relieving symptoms of anxiety.
Another way in which CBD interacts with different ion channels is by binding to TRPV1 receptors. TRPV1, or “transient receptor of potential cation channel subfamily V,” is also known as a vanilloid receptor. These are responsible for how the body reacts to pain, inflammation, and changes in temperature.
In some cases, CBD can block G-protein-coupled receptors. This is true of GPR55, an orphan receptor. It has been given this name because it does not have a known natural binding compound. GPR55 is found in the cerebellum, or the back of the brain. It helps regulate things such as blood pressure. GPR55 is also found on osteoclast cells ,and thus researchers are exploring the potential for CBD to alter bone density.
Another family of receptors that are activated by CBD are PPARs, or peroxisome proliferator activated receptors. These have an anti-proliferative effect. They also may help regress lung cancer cells and break down amyloid-beta plaque. PPARs have been linked to helping relieve symptoms related to Alzheimers’ disease. Medical researchers are also exploring how diabetes patients may also benefit from the way CBD intervenes with nuclear receptors. That’s because PPARs help manage the genes responsible for insulin sensitivity, the uptake of lipids, and energy homeostasis.
CBD as an Inhibitor
CBD binds to nuclear receptors through a fatty acid binding protein, which also lets through lipid molecules, THC ,and other endocannabinoids within the cell. CBD helps modulate receptors, which in turn manages mitochondrial activity such as gene expression. Since CBD has an affinity with certain fatty acid binding proteins, it can also help transport molecules. CBD interferes with the breaking down of anandamide. Because cannabidiol reabsorbs the neurotransmitter and inhibits its breakdown, it may elevate endocannabinoid levels in each synapse of the brain. As a result, endocannabinoids may be enhanced, which could assist in protecting the brain from the effects of a seizure.
In addition to this, CBD inhibits the absorption of adenosine, causing its receptor activity to be increased. Adenosine receptors A1A and A2A are what promote cardiovascular health, blood flow in the coronary arteries, and oxygen consumption of the heart’s muscular tissues. Medical research is underway to determine if these properties may allow CBD to produce anti-anxiety and anti-inflammatory effects throughout the entire human body.
CBD as an Allosteric Modulator
CBD also plays an additional role—that of increasing or hindering a signal from being transmitted. It does so by redefining the receptor’s shape. Because of the way cannabidiol changes the signal strength that a receptor transmits to another cell, some researchers hypothesize that CBD may be a positive allosteric modulator with GABA receptors. These receptors respond to gamma-aminobutyric acid (GABA), a neurotransmitter and main inhibitor in a person’s nervous system. GABA receptors are found in the limbic system.
Psychoactive drugs like benzodiazepines help sedate a person because of how GABA receptors mediate their transmission. CBD may affect GABA receptors by changing them to enhance GABA transmission. If so, this could increase the calming properties of endogenous GABA, which could potentially reduce anxiety.
How Does CBD Affect GABA?
One report published in the National Center for Biotechnology Information studied the link between CBD and GABA receptors. Researchers used magnetic resonance to measure levels of glutamine and GABA on 34 male patients, half of which suffered from autism spectrum disorder. They did so after administering each study group 600 mg of CBD in one dose. The findings concluded that CBD does modulate GABA receptors. In the case of healthy patients, it increased. Whereas in patients with autism, it decreased. The difference between the two was described as significant by the researchers. As a result, they concluded that CBD affects GABA receptors, but the response differs between neurotypical human subjects and those with autism.
The ways in which CBD affects GABA receptors may be at the heart of its potential anti-anxiety properties. Gamma butyric acid receptors are neurotransmitters and are the main inhibitory chemical in the central nervous system. As a result, they slow brain activity. Glutamate, on the other hand, has an excitatory effect. Too much of it can cause anxiety.
GABA is just one example of a receptor that helps manage anxiety. Some people turn to benzodiazepines so that they can activate GABA receptors. Unfortunately, these drugs also come with some undesirable side effects. CBD, on the other hand, helps activate CB1 receptors, which could aid in reducing anxiety and stress. CBD may also impact 5-HT1A receptors, which help increase feelings of wellbeing. As for TRPV1 receptors, CBD could help regulate a different form of anxiety: the sort that stems from inflammation and chronic pain.
GABA receptors help keep a healthy balance between the two neurotransmitters and ensure proper brain function. CBD and the endocannabinoid 2-AG increase the production of GABA. Another study that had been conducted on mice further revealed the anxiolytic effect of CBD.
Interestingly, high levels of stress diminish GABA production. But its production went back to normal when introduced to an anti-inflammatory. Cannabidiol has potential to reduce inflammation in addition to calming the brain’s immune response. As a result, researchers were exploring the hypothesis that CBD affects GABA receptors in a way that may be beneficial to human health.
How Much CBD is Needed to Increase GABA?
Another study, whose results were published on NCBI’s website, shows how CBD’s calming effect increases until a dosage of 300 mg. From that point onward, cannabidiol can activate PPAR. Many patients in the study felt anxiety relief at a range of 40 mg to 100 mg. We must point out, of course, that this is simply the result of a single study. The FDA has not approved CBD as a treatment for anxiety, nor have they made any suggestions on specific dosages.
CBD’s Binding Affinity
Some medical researchers label cannabidiol as a negative allosteric modulator. This is not for GABA receptors, but CB1 receptors. They are found in the central nervous system as well as in the brain. Unlike THC, cannabidiol doesn’t bind directly to CB1 receptors. Instead, it diminishes the CB1 receptor’s ability to bind with tetrahydrocannabinol. CBD acts as an allosteric modulator by changing the shape of the CB1 receptors. As a result, THC’s psychoactive properties are reduced. This explains why a product like CBD isolate, although containing traces of THC, won’t “get you high”.
After reading this article, we hope you better understand how CBD affects GABA receptors. Although research is still underway to determine the complete effects of cannabidiol, many people are hopeful that it will one day be approved as a treatment for anxiety and many other conditions.