CBD Oil: Will it work for you?

CBD oil is marketed as a way to decrease inflammation and increase mood. But… not everyone gets great results with it.

Why do some people benefit greatly from CBD while others notice nothing? Your genetic variants play a role in how your body responds to CBD.

This article goes in-depth on research studies about CBD, the receptors that CBD binds to, and how your genetic variants could be influencing your response to CBD oil. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today. 

Cannabidiol (CBD): Does It Work?

Cannabidiol, abbreviated CBD, is a phytocannabinoid found in cannabis (marijuana) and hemp plants. It was first isolated from the plant in the 1940s, and scientists unraveled its structure in the 1960s. It is a colorless solid at room temperature and is insoluble in water.

CBD does not cause psychoactivity (feeling high). Instead, it is being used for various anti-inflammatory and antiepileptic properties.[ref]

It is legal to buy cannabidiol oil in many places, but state laws can vary depending on whether the CBD is derived from hemp or cannabis. CBD derived from cannabis is often called ‘full spectrum’.

Cannabis research initially focused on THC, the psychoactive part of the plant, and the CBD component was pretty much ignored for many years. The past decade has seen an explosion of research on CBD, with several thousand studies referencing it now.

Interesting fact: Cannabis has been used for thousands of years. Researchers have analyzed cannabis found in a 2700-year-old grave of a shaman in China.[ref]

Your Endocannabinoid System

The psychoactive component of cannabis, Δ⁹-THC, binds to cannabinoid receptors in the body. These receptors are part of our endocannabinoid system. Cannabinoid receptors aren’t there just to bind to cannabis, of course. The endocannabinoid system regulates endocrine, immune, and brain functions. For example, it is involved in appetite control (why cannabis gives some people the ‘munchies’).[ref]

The body produces an endocannabinoid called anandamide, which is a lipid-based neurotransmitter. Anandamide binds to the cannabinoid receptors in the central and peripheral nervous systems. It plays a role in regulating mood, appetite, memory, sleep, temperature, and the development of an embryo.

But… CBD oil doesn’t really activate the cannabinoid receptors. Instead, it acts on several other receptors and modulates the response of the cannabinoid receptors.

Research Showing the Benefits of CBD Oil

Looking beyond the advertising hype, here is what research studies on CBD show:

Anti-inflammatory:
CBD is anti-inflammatory in the colon. A study used sections of inflamed colons from IBD, appendicitis, and bowel cancer patients to test the effects of CBD. The study found that CBD acts as an anti-inflammatory and prevents an increase in cytokine production in inflamed colon cells. It did not affect cancer cells in this study.[ref]

Pain:
CBD has been shown in animal studies to reduce pain. It may go along with the anti-inflammatory properties or may act through a different mechanism.[ref] CBD has also been shown to affect pain and inflammation when applied topically.[ref]

Addiction:
Animal studies have indicated that CBD might change behavior in heroin addiction. More research is needed on this, but CBD may be something to add to addiction rehab programs. [ref]

Intestinal Barrier: 
Studies show that CBD can improve intestinal barrier function (reduce leaky gut!) for people with C. difficile infection.[ref]

Anxiety and Depression:
Several animal studies show that CBD may effectively relieve some symptoms of anxiety. A case study of a child with PTSD and sleep problems found that CBD was safe and effective for reducing anxiety. (More research must be done to know the full effects on kids!) [ref][ref][ref]

Several animal and human studies have shown that CBD has an antidepressant effect on some people.[ref][ref]

Epilepsy:
Some specific types of epilepsy can be treated using CBD.[ref][ref][ref] A randomized controlled trial for Dravet syndrome found that cannabidiol reduced seizure frequency more than placebo, but there was also a higher rate of adverse events.[ref]

Apoptosis:
Research shows that CBD oil induces apoptosis (cell death) in cervical cancer cells.[ref]

Acne:
A cell culture study shows that CBD oil may effectively treat acne vulgaris.[ref]

Sleep: 
A study involving 72 adults found that CBD helped sleep scores in about two-thirds of patients. The study participants all were dealing with anxiety, and anxiety scores also decreased for the majority of the participants.[ref]

Antimicrobial:
Cannabidiol has been shown in several studies to act against biofilms and be antimicrobial for Gram-positive bacteria. The research points to membrane disruption as the mechanism of action.[ref]

Peripheral neuropathy:
Topical cannabidiol for peripheral neuropathy was investigated in a clinical trial. The results showed: “There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study.”[ref]

Caution and Safety:
A cell study published in 2019 shows that CBD could cause DNA damage. DNA damage is never good. Of course, the study needs to be replicated, but it does raise some questions about CBD being entirely safe.[ref]

Most animal and human studies show CBD oil to be safe and well-tolerated (even at high doses of up to 1,500mg/day). There have been side effects shown, such as interactions with medications. It is easy to think – ‘oh, this is just something natural from a plant’ – but instead consider it as a medication regarding interactions with other meds you are taking.[ref][ref]

CBD receptors: How CBD Actually Works

Cannabidiol interacts with various receptors in the body — which explains the great variety of different conditions that it treats. Due to genetic variants in the receptors, these different receptors may also explain the differences in effect people see when using CBD oil.

A little background on receptors:
Receptors are made up of a protein complex. The ligand is the molecule that binds to the receptor and activates it (e.g., cannabidiol). The metaphor commonly used to describe receptors and ligands is a lock and a key.

The ligand binds to a binding site on the receptor and activates it – like a key fitting into a lock.

• A molecule that fits into the receptor but doesn’t activate it – blocks the keyhole – is referred to as an antagonist of the receptor.
• A molecule that fits in the keyhole and activates the receptor (but isn’t the normal ligand) is an agonist.

This lock and key concept can get a little more complex when a molecule can bind to part of a receptor and cause the natural ligand to be either more active or less active — this is called an allosteric modulator. A positive allosteric modulator causes the receptor to be more active.

CBD binds to a serotonin receptor:

Cannabidiol interacts with the serotonin receptor 5-HT1A. It may be why, for some people, CBD oil reduces depression.

There is some question as to whether CBD binds directory to the serotonin receptor or whether it acts as an allosteric modulator, enhancing the signal of endogenous serotonin. Most of the recent studies point to it being an allosteric modulator, binding to the receptor and modifying serotonin uptake.[ref]

Animal studies show that the effect on the serotonin receptor is not due to any effect from the cannabinoid receptor (CB1). One study showed that repeated CBD dosing for seven days “reduced nerve injury-induced anxiety-like behavior”. In other words, surgery was performed on the animals to produce nerve pain, and seven days of CBD decreased the nerve pain and anxiety from the pain. The interaction with the serotonin receptor was the cause of the anti-anxiety effects.[ref][ref][ref][ref]

Reducing nausea: While people commonly think of serotonin receptors in the context of neurotransmitters and depression, the body also has serotonin receptors in the gut. For people with cancer, chemotherapy often causes nausea. It is triggered by serotonin released in the small intestines. Cancer patients often use cannabis (with THC and CBD) to counteract nausea.

An animal study showed that CBD suppresses vomiting.[ref]

TRPV1 (Pain receptor): Activated by CBD

CBD also activates and desensitizes the vanilloid 1 receptor (TRPV1).

The TRPV1 receptor is involved in the regulation of body temperature and in sensing heat and pain. Temperatures over 109 degrees F activate the receptor. Capsaicin, the hot spice in chili peppers, and isothiocyanate, which causes the hotness of wasabi and mustard, also activate the TRPV1 receptor.

Desensitization of the receptor, such as through repeated exposure to capsaicin, decreases its activity (and pain, such as from neuropathy).[ref]

CBD only acts on the vanilloid receptor at certain dosages, and the dose effect is thought to be a U-shaped curve. High doses of CBD show no effects on TRPV1 receptors.[ref][ref]

Related article: Specialized Pro-resolving Mediators also interact with TRPV1

CBD binds to GPR55

The G-protein coupled receptor 55 (GPR55) is a receptor found in the central nervous system and the intestines, bone marrow, endothelial cells, and platelets.

GPR55 is similar to the cannabinoid receptors (CB1 and CB2) but differs structurally in a couple of ways. CBD is a GPR55 antagonist — it blocks the function of the receptor. GPR55 is involved in axon growth and the wiring of the brain.[ref]

It is thought that CBD’s benefit in treating epilepsy is due to blocking GPR55 and decreasing the excitation of certain neurons. A lot of research is still going on about this topic, but it is exciting to see how a natural substance can be used for children with epilepsy.[ref]

Adenosine 2A Receptor: CBD and ADORA2A

The adenosine 2A receptor is one of several different adenosine receptors in the body. Adenosine is a molecule in the body that does many different things, including being a part of ATP (adenosine triphosphate) and cellular energy.

Adenosine also acts in cellular signaling and is a neuromodulator that promotes sleep. Caffeine binds to the adenosine 2A receptor, causing people to feel more awake. Additionally, the adenosine 2A receptor is involved in the immune system and cancer immunomodulation.[ref]

CBD has been shown in several recent studies to bind to the adenosine 2A receptor. In cannabis use, CBD blunts cognitive impairment that Δ⁹-THC causes — through its effects on the adenosine 2A receptor.[ref]

An animal study of lung inflammation found that CBD decreased the effects of the pro-inflammatory cytokines (TNF and IL-6) and other inflammatory pathways. This study clearly showed that the anti-inflammatory effects of CBD were due to the adenosine 2A receptor.[ref][ref]

A study showed that injecting CBD into the hypothalamus increases adenosine levels in the brain.[ref] This may affect sleep… One trigger for needing sleep is the accumulation of adenosine in the brain. And increased adenosine has been shown to increase non-REM sleep while decreasing REM sleep.[ref]

A rat study of CBD oil at two different concentrations showed that the total amount of sleep increased while higher doses delayed the onset of REM sleep.[ref]

CBD has also been shown to protect against heart arrhythmia (ventricular). It was shown to be through the activation of the adenosine A1 receptor.[ref]

CBD and GABA

There is some evidence that CBD acts on the GABA receptors also. GABA is the inhibitory neurotransmitter that blocks neurons from firing. It keeps the neurons from being overexcited.

A study using magnetic resonance spectroscopy to measure glutamate and GABA levels in the brain showed some interesting results. The study compared 17 neurotypical men and 17 autistic men at baseline and after a single dose of 600mg of CBD oil. The CBD increased subcortical glutamate but decreased cortical glutamate in both groups. But the results for GABA showed significant differences between neurotypical and autistic men. The GABA levels in neurotypical men increased after CBD, but the opposite happened for autistic men, with a (statistically) significant decrease.[ref]

Platelets, Arachidonic Acid Release, and CBD

Both CBD and THC stimulate the release of arachidonic acid in platelets. CBD is a more potent activator of arachidonic acid than THC. Arachidonic acid is a polyunsaturated fatty acid that can be part of the cell membrane. It is also used to synthesize anandamide, the endocannabinoid our body produces that binds to the cannabinoid receptor.[ref] The release of arachidonic acid may increase anandamide, thus creating some of the pleasant effects associated with CBD.

Lifehacks:

Buying Good CBD Oil:

What kind of CBD to buy – and where?? 
Honestly, I am not an expert on this and don’t want to steer anyone wrong. My only advice is to go with a reputable company with reviews from real people (not MLM shills).

A new startup company, Flower & Tonic, does independent lab testing of CBD products off the shelf. You may want to check that out — I like the idea of independent reviews based on testing products purchased at retail stores.

Dosages of CBD for different mood disorders:

Related Articles and Topics:

Cannabis and your genes: effects, dependency, and risks
Cannabis is now legal for medicinal or recreational use in many U.S. states and Canada. Many people are using cannabis (marijuana) for various reasons – from enjoyment to pain management to the side effects of chemotherapy.

Serotonin: How your genes affect this neurotransmitter
Serotonin… a word that brings to mind a commercial that might show our happy brain neurons bouncing serotonin between them. There is a lot more to this molecule than most of us realize! This article covers how serotonin is made in the body, the transport of serotonin, and the receptors needed to complete the pathway.

HPA Axis Dysfunction: Cortisol and Stress
Cortisol is a hormone produced by the adrenal glands in times of stress, and it also plays many roles in your normal bodily functions. It is a multi-purpose hormone that needs to be in the right amount (not too high, not too low) and at the right time. Your genes play a significant role in how likely you are to have problems with cortisol.