CBD Information Guide

HOW DOES CBD WORK?

The endocannabinoid system - or ECS - regulates many bodily functions, such as sleep, pain, mood, appetite, and immune system responses. CBD blocks harmful compounds from entering these receptors.

Patients usually take around 20 to 25 mg/kg/day of CBD for clinically diagnosed diseases, like Lennox-Gastaut syndrome, tuberous sclerosis, or similar conditions in randomized controlled trials. However, this dose is substantial. Many officials in multiple Western countries suggest people take 70 mg daily (as the upper limit), and experiment to see what works for them. 

Researchers are currently exploring areas where CBD may offer therapeutic benefits, including isolates, distillates, and full-spectrum options that contain other chemicals from cannabis plants. These studies are growing in number every year, covering multiple conditions, including physical and psychiatric disorders (such as psychosis, bipolar disorder, Parkinson’s, and anxiety-related conditions). 

How is CBD Absorbed?

Understanding CBD absorption provides deeper insights into how CBD works and why it is so effective. 

Research shows that CBD is a lipophilic (fat-loving) molecule. As such, it does not dissolve in water. Instead, cannabinoids must attach to a fatty acid-binding protein to pass through the membranes of our cells. 

Once inside the cell, the story becomes more involved. Fatty acid amide hydrolase, a metabolic enzyme, starts to break down cannabidiol. From there, CBD can begin interacting with the receptors and compounds in our bodies. 

Research is ongoing, but studies show that CBD metabolism occurs mostly in the liver via cytochrome P450 enzymes, like CYP2A4 and CYP2C19. These investigations now better understand the process of transformation CBD undergoes and how it gets into all the body’s systems, turning into more than forty metabolites with purported metabolic effects. 

Fatty acid amide hydrolase (FAAH) isn’t entirely efficient, though. While it can break down CBD in some settings, it can exhibit lower activity in others. As such, it may help elevate anandamide levels (the feel-good hormone) by pushing CBD to compete for FABP binding. Again, research is ongoing, but it suggests CBD works in a round-about way: preventing the activity of metabolic pathways designed to return the body to homeostasis and indirectly allowing a rise in happy hormone activity. 

In summary, CBD absorption works via a three-step process: 

1. Transport across the cell membrane due to CBD’s fat-loving nature and ability to bind using fatty acid-binding proteins (FABPs)

2. Metabolism inside primarily liver cells, particularly cytochrome P450 enzymes into various metabolites

3. Interaction by CBD and its metabolites with relevant receptors in the body, including CB1, CB2, TRPV1, 5-HT1A, and so on

This multi-step process is still under review and you may read different mechanisms elsewhere. However, this description comes from an appraisal of the most recent science. 

The Endocannabinoid System

As we already mentioned above, CBD is one of over 100 compounds called cannabinoids that come from the hemp plant. Among these are CBG, which is the preliminary form of CBD, THC, and CBC. From THC also comes CBN, which is gaining some ground.

The human body already produces some cannabinoids —these are called endocannabinoids. Since these compounds are naturally produced in the body, the body also has a system for dealing with the signals it receives from cannabinoids. This system is called the endocannabinoid system, or ECS. The ECS regulates many bodily functions, such as sleep, pain, mood, appetite, and immune system responses

The receptors in the ECS are divided into two categories: CBD1 and CBD2. CBD1 receptors are typically found in the nervous system, with a small proportion found in the kidneys, lungs, or liver. These receptors are the ones known to interact with the neurotransmitters and affect sensations like appetite, concentration, and more.

CBD2 receptors, on the other hand, are crucial to the immune system. They modulate the pain sensation and other immune responses.

According to studies, CBD may not bind to the ECS itself — but activates or inhibits other compounds and receptors. This may also be why CBD doesn’t produce any psychoactive effects. Delta 8 THC, another one of CBD’s relatives, is psychoactive. You can learn more about how delta 8 and CBD relate in this post.

For example, Pertwee (2008) showed that CBD weakly binds to CB1 and CB2 receptors but is instead a negative allosteric modulator, meaning it is a compound that decreases receptor activity by binding to a different site other than the one occupied by the neurotransmitter. This action potentially deadens the capacity of the receptor to bind to some compounds instead of others. For example, Pertwee showed that CBD changes the signaling of CB1 receptors in various brain regions, altering their response to anandamide. Investigations suggest that CBD can “potentiate” or enhance the body’s natural response to its endogenous feel-good chemical production, explaining why the compound doesn’t produce the same psychoactive effects as THC. 

Further research by Leweke and colleagues shows that CBD boosts endocannabinoid signaling by preventing anandamide breakdown. It does this by stopping fatty acid-binding enzymes like FAAH from getting at the molecule. Preventing this degradation allows anandamide levels to remain high, improving the overall capacity of the endocannabinoid system. Researchers, like Leweke, believe this system is responsible for CBD’s beneficial effects on conditions like psychosis, anxiety, and inflammation. It targets the root of the imbalance by enabling more anandamide to remain in the system for longer. 

Therefore, science suggests that CBD acts on the endo-cannabinoid system through two distinct channels: 

1. Through allosteric modulation of cannabinoid receptors (preferentially binding to specific sites that adjust their signaling)

2. Inhibiting the degradation of the feel-good hormone, anandamide

As such, recent science demonstrates that CBD does not interact as a classical agonist of CB1 and CB2 receptors. Instead, its power seems to come from its ability to fine-tune the endocannabinoid system, something that makes it special and quite different from THC. 

How Does It Affect the Body?

The extent to which CBD can affect the body is profound. Dozens of studies suggest that the compound is highly effective in treating an array of disorders, providing hope to vast swathes of the population. 

One study shows that, at high concentrations, CBD can directly activate the 5-HT1A (hydroxytryptamine) serotonin receptor. This receptor is a factor in a large range of conditions and symptoms, such as nausea, pain, sleep, addiction, appetite, and anxiety.

Another study shows how CBD can bind to TRPV1 receptors. TRPV1 is known for mediating temperature, inflammation, and pain.

By stimulating the adenosine receptor, CBD can promote dopamine. Dopamine affects processes like motor control, motivation, reward, and cognition. CBD may also promote glutamate, which involves learning and memory production.

CBD can interact with the GABA-A receptor to enhance its ability to bind with GABA. GABA is the main inhibitory neurotransmitter in our nervous system, and CBD can allow the GABA-A receptor to amplify the natural calming effect of GABA, which helps address anxiety.

Because of these “mechanistic” chemical interactions, CBD may offer significant improvements in clinical endpoints. For example, studies looking at CBD’s ability to modulate endocannabinoid signaling in psychosis and schizophrenia find that it improves anandamide signaling in these conditions. Studies show that it inhibits anandamide breakdown, reducing the endocannabinoid dysregulation seen in psychosis patients.

Furthermore, several randomized, double-blind, placebo-controlled trials show that CBD reduces seizure frequency in treatment-resistant conditions, like Lennox-Gastaut and Dravet syndromes. These diseases often lead to uncontrollable muscle responses throughout the body, but CBD may prevent the worst symptoms. Researchers aren’t entirely clear why, but they think it may work through GABA modulation and TRPV1 channels, reducing endocannabinoid destruction. This process then prevents convulsions in some patients.

Lastly, individuals with chronic pain and inflammation may also benefit from taking CBD. Cannabidiol has pain-reducing and anti-inflammatory effects by acting through several channels, including PPARγ receptors which deal directly with inflammatory gene expression, and other mechanisms, like FAAH inhibition, which work differently. Researchers believe this multi-modal action is what gives CBD its tremendous efficacy. Like varied whole-food diets, CBD works across multiple pathways, allowing it to attack the root causes of pain and inflammation from different angles. 

Unfortunately, most research into CBD focuses on mechanisms or rare conditions, like Lennox-Gastaut and Dravet syndromes. As such, the quality of science suggesting its efficacy for more general conditions remains limited. However, the mechanistic evidence is strong. CBD interacts with numerous cannabinoid targets (like its negative allosteric effects on CB1 and CB2) and through non-cannabinoid pathways, like TRPV1, 5-HT₁A, PPARγ, and GABA_A with known links to pain, inflammation, and anxiety. 

CBD Side Effects

With all these complex chemical reactions mentioned in the prior sections, it’s understandable if you’re curious about side effects. 

Are any side effects guaranteed if you take CBD? Does it depend on your unique body system, usage patterns, as well as any other health conditions you may have? All yesses! The best way to manage any potential side effects is to keep your physician in the loop.

The good news is that CBD side effects are minimal compared to other components of the cannabis plant, including THC. Researchers believe the compound is generally safe when taken in sensible doses, which is why it is now commonly available.

Some side effects of CBD include, but are not limited to the following:

• Extreme drowsiness

• Lethargy

• Upset stomach

• Diarrhea

Most mild to moderate adverse events occur in trials on epilepsy where participants take CBD megadoses. The most common disturbances include diarrhea, changes in appetite, and fatigue. These likely relate to large amounts of CBD compounds coming into contact with nerve cells in the intestinal walls. 

Effects on the liver are also sometimes severe. High doses of CBD can lead to increases in inflammation-indicating enzymes on liver profile tests, like ALT and AST, but these are worse in patients taking mental health drugs, like valproate and clobazam. 

Finally, CBD can inhibit enzymes such as CYP3A4 and CYP2C19 we mentioned earlier. Preventing these from acting can increase blood levels of drugs they break down, meaning an increase in the concentration of any co-administered medicines. As such, it is always worth telling your doctor if you decide to use CBD.

Though side effects aren’t fun, they’re not guaranteed. They’re certainly not guaranteed if you do your best to follow product instructions, either. Wondering how CBD will make you feel in general? This comes down to a variety of factors, such as:

• The type of product you take or use

• Your unique body system or biome

• The symptoms you’re experiencing

You may also wonder if CBD causes any sort of body “high.” Though CBD can address symptoms of anxiety, as well as boost healthy sleep patterns when combined with ingredients like melatonin, CBD still does not affect you as THC would.

Summary To This Guide

This guide delved into the science of CBD and the effects it has on the body. As you will have noticed, it is a complex field with many moving parts. Furthermore, misunderstanding about the role of CBD and the action it has on the body is rife. Many guides simply do not understand how it works or the latest science.

Therefore, be careful when reading blogs or taking CBD. Always stick to the recommended doses and work with a physician if you are taking any other medications, especially those designed to treat mental health conditions like bipolar disorder, anxiety, and psychosis.