How Does CBD Work?

Cannabinoids (such as CBD) influence a wide array of bodily functions. Endocannabinoids ('endo' meaning 'inside') are cannabinoids made naturally inside your body. These closely resemble the cannabinoids that occur in hemp (also known as phytocannabinoids).

Endocannabinoids are created locally and on-demand to target acute cellular issues (contrast this with hormones, for example, which are synthesized in a gland and then widely circulated throughout the body). Anandamide, the most notorious endocannabinoid, is responsible for regulating: ^[5]

• Pain
• Pleasure
• Wakefulness
• Reward pathways
• Reproduction
• Cognition
• Motor functions
• Appetite
• Mood
• Fear
• Attention
• Immune function

CBD interacts with cannabinoid receptors and enhances their activity - while at the same time boosting endocannabinoid levels.

For example, CBD inhibits FAAH (Fatty Acid Amide Hydrolase), an enzyme that breaks down anandamide. Essentially, CBD directly increases anandamide levels in the human body.^[6]

CBD (and other cannabinoids) aren't the exclusive ways to nourish the ECS, however. Essential fatty acids, cacao, herbs, spices, and teas either have building blocks of endocannabinoids or compounds that bind to our cannabinoid receptors and offer beneficial effects.^[7]

While the purpose of cannabinoids in plants remains unclear, the most popular hypothesis suggests they act to protect the plant from insects, bacteria, fungi, ultraviolet radiation, and drying.

Cannabinoids are 'retrograde transmitters' as they travel backward against the flow of typical neurotransmitters (serotonin, dopamine, GABA, and glutamate). In this sense, you can imagine cannabinoids as a 'flow-control' mechanism. ^[8]

For example, imagine a presynaptic cell whose function is releasing dopamine. Typically, cannabinoid receptors will be densely populated on this neuron close to where dopamine is released. To avoid excessive stimulation, the tissue surrounding the postsynaptic neuron will synthesize a cannabinoid and release it. As this cannabinoid binds to the receptors on the presynaptic cell, dopamine flow slows, and you achieve homeostasis.

This process highlights another critical difference of cannabinoids from traditional neurotransmitters (which the body manufactures and stores in the presynaptic vesicle for later use). Instead, cannabinoids are biosynthesized on-demand and are an integral part of nearly all human tissues. ^[9]

You can imagine why a lack of internal cannabinoids might cause your mind and body to run haywire - imagine a busy four-way intersection with malfunctioning stop lights - absolute chaos. A great example is in the case of acne; cannabinoid receptors are intimately intertwined with sebaceous glands - a lack of cannabinoids to regulate this oil-producing gland can wreak havoc that all too many know well.^[10]

Clinical Endocannabinoid Deficiency (CED) is thought to be at the root of many chronic health conditions that have, up until now, been thought untreatable.^[11] This new diagnosis is gaining more and more traction among the medical and scientific communities.

There are four distinct ways that your endocannabinoid system can be out of balance:

• Excessive enzymes interrupting endocannabinoids
• Insufficient endocannabinoid production
• Inefficient signaling between cannabinoid receptors
• Lack of cannabinoid receptors

Fortunately, CBD helps to mitigate all four of these problem areas.

• Adenosine Enhancement: By inhibiting ENT1, CBD inhibits adenosine re-uptake. Extracellular adenosine offers general cellular protection in the body by increasing oxygen supply, promoting new blood vessel growth, and triggering other beneficial physiological processes. ^[12]
• PPAR-gamma Activation: Located in each cell's nuclei, PPAR-gamma receptors moderate insulin sensitivity, dopamine release, fat uptake, and also degrade beta-amyloid plaque. Activation of PPAR-gamma receptors by CBD could be why many people may experience benefits with weight and blood sugar management, as well as Alzheimer's.^[13]
• FAAH Inhibition: Fatty acid amide hydrolase is the enzyme responsible for breaking down anandamide ('the bliss molecule'), a primary endocannabinoid in the body. CBD inhibits FAAH, allowing for increased anandamide levels - offering myriad benefits thanks to anandamide's activity at CB1/CB2 receptors.
• GPR55 Antagonism: Ubiquitous in the brain, GPR55 receptors (believed by some experts to be the third type of cannabinoid receptor) influence bone density and blood pressure (among other things). CBD likely influences blood pressure via this receptor (be careful, very high amounts of CBD can lower blood pressure too much, causing lightheadedness). Activation of GPR55 can contribute to high blood pressure, cancer growth, and osteoporosis - which is why 'antagonism' (reduced activity) of this receptor by CBD is a good thing.^[14]
• D2 Dopamine Binding: This receptor is often the target of psychiatric medications and may explain why some people taking CBD may experience relief from mood disorders and anxiety.
• TRPV1 Activation: Famous for being the target of capsaicin (the active, spicy compound in cayenne peppers), TRPV1 helps regulate body temperature, pain perception, and inflammation processes. Cannabinoids bind to this receptor, potentially explaining the antihyperalgesic benefits some may experience when using CBD Oil. ^[15]
• 5-HT1A Activation: High amounts of CBD have been shown to activate the 5-HT1A receptors, a crucial neuron that regulates everything from addiction and appetite to nausea and vomiting. Cannabinoid activity at this receptor could cause all the anecdotal reports of reduced symptoms of behavioral and cardiovascular conditions while taking CBD Oil.^[16]
• Glycine Potentiation: Like GABA, glycine receptors have inhibitory actions, meaning that they help calm everything down. Not only do glycine receptors help calm the nervous system, but they are also central in assisting the body to detect pain. By potentiating these receptors, CBD could offer many benefits to stress levels, as well as chronic pain.^[17]

CBD also has activity at the mu and delta opioid, 5-HT3A, GABA-A, and A7-ACHR receptors.^[18],^[19],^[20],^[21]

While we have seen a significant increase in the undertaking and publication of quality, evidence based studies on medicinal cannabis, we are just scratching the surface in understanding how and to what extent these cannabinoids work in a human body. As such, more research is needed to determine the efficacy of cannabinoids in improving human health.