CBD, or cannabidiol, may prompt various reactions as a result of its potential anti-inflammatory, antianxiety, antioxidative, and anticonvulsant qualities. CBD has the ability to utilise many molecular pathways to produce these results, which makes it a pleiotropic drug. Research has shown that it may be an extremely beneficial treatment option for patients with Parkinson’s disease, anxiety, epilepsy and gastrointestinal conditions.
We’ve put together this scientific overview to answer the following question -
How does CBD work in the brain and body?
The Endocannabinoid System
The endocannabinoid system (ECS) is a vastly complex system that is known to interact with cannabis compounds. Responsible for regulating a wide range of biological responses such as mood, inflammation, pain, memory and appetite, the endocannabinoid system does this by sending messaging chemicals (endocannabinoids) all around the brain and body to promote homeostasis, once its receptors have been activated.
There are two main receptors in the ECS, called cannabinoid 1 receptor (CB1) and cannabinoid 2 receptor (CB2). The body produces two known endocannabinoids, anandamide and 2-AG, to naturally bind to these receptors. This then sends signals that trigger biological responses, such as increasing hunger or decreasing the sensation of pain.
According to the experts, although they are so similar in chemical structure, the phytocannabinoids that cannabis produces (which include CBD and THC) interact with the endocannabinoid system in different ways upon entering the body. THC is known to bind to CB1 and CB2 receptors all over the brain and body, which can trigger various reactions such as reducing nausea.
However, CBD is thought to act differently. Instead of activating cannabinoid receptors directly, CBD acts as an allosteric modulator, and influences the activity of endocannabinoids. This is because CBD has a reduced ability to bind effectively to cannabinoid receptors when compared to THC, and so instead it focuses its attention on other receptors and the signalling pathways that endocannabinoids interact with.
As CBD’s exact mechanisms of action are still being uncovered, there has been debate amongst scientists surrounding the possible existence of a third type of cannabinoid receptor that CBD could interact with.
However, as this theorised receptor is still yet to be discovered, the scientific community generally agree that cannabidiol is able to have its effects on the body primarily by reducing the natural enzymatic breakdown of our own endocannabinoids, or by impeding the messages sent from neurotransmitters around the body.
So, how does CBD work?
CBD is taxied into cell membranes by fatty acid-binding proteins. Once inside the membrane, CBD can then interact with lots of different receptor types, causing a variety of potential effects on humans. This is the same way endocannabinoids are transported around the body, and so when CBD is consumed, the delivery of naturally produced cannabinoids can be delayed, raising their overall levels in the body. For this reason, CBD is known as a reuptake inhibitor.
TRPV1 or Vanilloid receptors are a type of receptor that is naturally activated by anandamide to regulate pain perception and inflammation. CBD can also directly bind to TRPV1, which may give it the ability to interact with these functions and alleviate pain or inflammation levels in the body. High concentrations of CBD have also been shown to activate serotonin receptors in the nervous system, which researchers believe may be the reason it produces the antianxiety effects that are associated with its administration.
Much like Valium, CBD has also been shown to interact with GABA A receptors, which may increase the binding affinity for neurotransmitters like GABA. This naturally promotes a relaxing effect, and this interaction has also been linked with the anticonvulsant and anxiolytic properties of CBD.
Here, Cannabidiol is assumed to act as a positive allosteric modulator, altering the shape of these receptors, which amplifies the benefits of GABA. CBD has also been shown to change the shape of CB1 receptors, however, in this case, CBD is a negative allosteric modulator – because this shape change weakens the receptor's binding affinity to THC.
Unlike TRPV1 and serotonin receptors, research suggests that CBD might actively block GPR55 or orphan receptors in the brain. Named so because scientists are unsure whether they belong to a family of receptors or not, orphan receptors regulate many processes including bone density and blood pressure. The over-activation of these receptors has been linked with the development of osteoporosis, but this research proposes that when GPR55 receptors are blocked by CBD, it can reduce this risk. By impeding these receptors, CBD has been shown to have the possible ability to decrease bone loss levels.
Further effects are attributed to the interaction CBD has with PPARs, a type of receptor that lives in the nucleus of different cells. These cells are often considered an extension of the endocannabinoid system. Also associated with the development of Alzheimer’s Disease, these receptors are known to regulate insulin sensitivity, lipid uptake and homeostasis.
Benefits of CBD
Because CBD is showing the possible ability to influence such a diverse range of neurotransmitters and their signalling pathways, research suggests a plethora of health benefits may be associated with this phytocannabinoid1. This can be seen in the findings of a recent study from the US that analysed cannabidiol’s effects on patients with osteoporosis, rheumatoid arthritis and other autoimmune arthritis conditions. The results showed an average improvement of 86% in pain, and 66% in both inflammation and sleep quality after using CBD.
In 2020 another study reported improvements in patients with peripheral neuropathy when treated with CBD. This included a reduction in cold or itchy sensations, as well as in the sharp pains that patients with nerve damage typically experience. The neuroprotective properties of cannabidiol have also been demonstrated in the regulation of inflammation and oxidative stress, so, CBD treatments may offer relief to patients with Parkinson’s Disease.
Other trials that investigate the efficacy of cannabidiol treatment in rare forms of childhood epilepsy also display impressive results. One study in 2018 asked caregivers to record the effects CBD had on treatment-resistant epilepsy, after 12 weeks the participant's average monthly convulsion seizure rate had fallen by 51% and their total seizure rate also reduced by 48%.
CBD has also been shown that it might offer relief to patients with anxiety in several clinical trials. One example is this 2022 study published in Communications Medicine, where patients with moderate to severe anxiety reported an 80% reduction in BAI scores (Beck Anxiety Inventory) and a 70% reduction in OASIS scores (Overall Anxiety Severity and Impairment Scale). The patients in this study were treated for four weeks and consumed 10 mg of CBD three times a day. All patients found an improvement in their anxiety within three weeks and also did not report experiencing any severe side effects.
Potential side effects of CBD
Like most health, wellness, or medical products, there are some known side effects associated with the administration of CBD. The most common are relatively minor adverse reactions that include feeling slightly nauseous, irritable, or fatigued, but there are more serious side effects linked with CBD. These include negative reactions with certain prescription medications and blood thinning. High doses of CBD have also been linked to abnormal blood results during liver exams, but this is also seen in patients using over-the-counter medications like paracetamol or ibuprofen.
When taken with other medications, CBD has to compete for the enzymes in the liver that are designed to break down drugs, which sometimes hinders the absorption rate of the other medications and their subsequent efficacy. Although this reaction is not specific to CBD and can also be seen when certain foods are eaten at the same time as these medications, like grapefruit, it is important to inform your doctor and follow their clinical guidance when taking CBD alongside other medications.
Conclusion
When considering the potential benefits of using CBD, it is essential to keep in mind that there are still many unknowns surrounding this intriguing cannabis compound. From the nature of how it interacts with different receptors and enzymes in the body, to its efficacy in treating certain conditions, there is still much research to be done on this subject before any definitive conclusions can be made.
That being said, as more studies are published and our understanding of cannabidiol increases, so too will our knowledge of its therapeutic properties and possible applications. In particular, CBD treatments have shown promise when targeting pain or inflammation, as well as anxiety, depression, and seizures. When coupled with its low toxicity profile and lack of major side effects, CBD may prove to be an attractive option for many individuals looking for relief from various symptoms or conditions. However, further study will be needed to fully understand the effects of CBD and whether it is a viable treatment option.
It is important to seek clinical guidance before you consider taking CBD as a medicine or supplement.
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