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The Endocannabinoid System – What You Should Know

Your endocannabinoid system is a complex network that regulates mood and inflammation, amongst other things.

Discovery of the Endocannabinoid System

In 1988, scientists made their first discovery of a cannabinoid receptor in the brain of a rat. This discovery was very significant in light research from by Israeli scientist Dr. Raphael Mechoulam. In 1964, Dr. Mechoulam became the first person to isolate and identify both THC and CBD from cannabis.

These two discoveries have allowed scientists to work towards a better understanding of the endocannabinoid system in humans and the way that the phytocannabinoids (cannabinoids derived from plants) THC and CBD, impact the receptors in our bodies and brains.

Humans actually produce similar substances naturally, known as endocannabinoids and these neurotransmitters perform a dazzling array of functions in our bodies.

Functions of the Endocannabinoid System

There are two main types of cannabinoid receptors, CB1 and CB2. CB1 receptors are mostly found in the brain, while CB2 receptors are primarily spread throughout the body.

In the brain, these CBD receptors exist with the highest concentration in the limbic system. The limbic system is not a separate part of the brain but is a collection of the hippocampus, hypothalamus, piriform cortex, amygdala, and more.

This crucial brain region is mostly responsible for emotion, mood, behavior, olfaction (smell), and memory. This may begin to explain why an underactive endocannabinoid system can increase anxiety, fear, and depression, while reducing the joy one may derive from food and sex.

When these systems are not functioning optimally, it can cause extreme stress in the body, a potential overproduction of cortisol (among other things), and host of complications which may include:

  • Insomnia
  • Brain Fog
  • Gastrointestinal Problems
  • Pain
  • Underactive Thyroid
  • Cold Hands and Feet
  • Frequent Urination
  • Weak Appetite
  • Low Blood Pressure

Clinical Endocannabinoid Deficiency (CECD)

Clinical Endocannabinoid Deficiency is a condition where an individual has a lower amount of endogenous cannabinoids than experts consider necessary to promote health and well-being.

Scientists now believe CECD may play a role in the following conditions:

  • Fibromyalgia
  • Irritable Bowel Syndrome (IBS)
  • Migraines
  • Multiple Sclerosis (MS)
  • Post-Traumatic Stress Disorder (PTSD)
  • Neuropathy
  • Huntington’s
  • Parkinson’s
  • Motion Sickness
  • Autism

These conditions often require a significant amount of medications to manage and treat. And while those medications are helpful, some of them come with a pretty significant of potential side effects. This list includes things like nausea, vomiting, abdominal pain, weakness, numbness, insomnia, suicidal thoughts, depression, anxiety, breathing difficulties and in some cases, death. These side effects are not incredibly common but they do exist.

But, there is good news. Because CEDC is considered a factor in so many illnesses, researchers across the globe are currently conducting studies to see if using a substance like CBD oil to elevate the cannabinoids in the body can have a positive impact on some of these conditions, providing relief without so many dangerous side effects.

The Human Body Produces Cannabinoids?

Anandamide is a neurotransmitter known as ‘the bliss molecule’ (ananda is a Sanskrit word that roughly translates to bliss). Anandamide is actually an endocannabinoid. It is a type of endogenous cannabinoids.

There are actually three varieties of cannabinoids — endogenous cannabinoids, phytocannabinoids, and synthetic cannabinoids. Let’s take a closer look at each:

Endogenous Cannabinoids: These are neurotransmitters produced within our bodies that bind to cannabinoid receptors in the brain, immune system, and other tissues. Examples include anandamide, 2-arachidonoylglycerol (2-AG), n-arachidonoyl dopamine (NADA), and virodhamine (OAE).

Phytocannabinoids: Refers to chemicals found in plants that, to varying degrees, mimic the action of our endogenous cannabinoids. Plants containing cannabinoids include:

Additionally, scientists have successfully generated yeast (Pichia pastoris) that can synthesize THCA.

Synthetic Cannabinoids:  Synthetic cannabinoids are essentially chemicals synthesized in laboratories, hopefully professional laboratories, that mimic our endocannabinoids. Most ‘synthnoids’ are named with an alphanumeric combination like JWH-007, JTE-907, or FAB-144.

Most health experts issue stern warnings about using synthetic cannabinoids, as studies link their usage to a myriad of long-lasting health problems.

Endocannabinoids perform in stark contrast to more well-known neurotransmitters such as serotonin, dopamine, and norepinephrine.

Dopamine, for example, is synthesized in advance, stored in the vesicle, and then released (in response to stimuli) from the presynaptic cell, where it crosses the synapse, lands on the postsynaptic cell, and causes activation.

Endocannabinoids, on the other hand, are integral components of cellular membranes that we appear to manufacture on demand. As they are hydrophobic, they cannot travel very far in the body and exert only local effects.

This limited effect makes endocannabinoids different from hormones, which are far-reaching and impact the entire body.

Additionally, endocannabinoids travel backward; first leaving the postsynaptic cell and ending at the presynaptic cell in areas where the axons are in high concentrations.

In essence, this allows the postsynaptic cell a sort of ‘flow control.’ This enables it to mitigate the flow of neurotransmitters coming from the presynaptic cell.

Anandamide

Anandamide is far and away the most widely researched endocannabinoid. It is an analog of THC and has a similar pharmacology, sharing roughly the same potency at the CB1 receptor.

It is synthesized in brain regions responsible for memory, motivation, and higher thought processes. Anandamide is crucial for :

  • Sleep
  • Pleasure
  • Reproduction
  • Cognition
  • Appetite
  • Mood
  • Fear
  • Pain
  • Attention
  • Immune Function
  • Movement

Anandamide has been found to reduce the proliferation of breast cancer cells, has anti-anxiety and anti-depressant effects, and increases neurogenesis. Anandamide also plays a significant role in memory formation and also is a factor in forgetting.

Anandamide, Exercise, and Going With the Flow

For quite some time, experts agreed that the world-renowned ‘runner’s high’ was due to the release of endorphins in the body after intense exercise.

However, in 2015, German researchers demonstrated that endorphin molecules are too large to pass the blood-brain barrier.

Through their experiment on mice, they concluded the mice’s ability to experience the runner’s high was mostly dependent on their cannabinoid receptors.

We all have experiences where we feel focused, happy and as though we are performing at our peak, which makes time feel like it’s just flying by.

This ‘flow state’ is the result of increased neurotransmitters, including anandamide.

Boosting Anandamide Levels With Food, ASA, and CBD Oil

A primary building block in the synthesis of anandamide is arachidonic acid (AA), a fatty acid found in various foods throughout nature. Primary sources include:

  • Chicken
  • Eggs
  • Beef
  • Fish
  • Pork

As with all bodily systems, diet and nutrition play a huge role in the healthy functioning of endocannabinoids. Individuals who consume plant-based diets, in particular, may have more difficulty with maintaining optimal anandamide levels.

Anandamide has a very short half-life (approximately 5 minutes) and is broken down by Fatty Acid Amide Hydrolase (FAAH).

Considering this, developing inhibitors of FAAH has become an area of much research.

CBD oil is considered a FAAH inhibitor. Other FAAH inhibitors include:

AM404 is the metabolic result of acetaminophen (Tylenol) combining with arachidonic acid (AA), and is also an agonist of both CB1 and CB2 receptors. This activity may explain the analgesic effects of acetaminophen.

While cacao has several known FAAH inhibitors, the stimulant theobromine contained in cacao that is thought to encourage the direct production of anandamide.

Anandamide, Pregnancy, Fertility, and Motherhood

The evidence points towards anandamide being the first line of communication between a mother and her unborn child. This particular endocannabinoid is vital for the healthy implantation of a young embryo in the wall of the uterus.

Researchers have further found that anandamide levels are highest during ovulation.

Interestingly, anandamide may also be a pivotal substance in triggering newborns to suckle at their mother's breast. When newborn mice received a potent CB1 receptor antagonist (SR141716A), the mice pups failed to latch at the mother’s breast and died within a week.

The central role endocannabinoids play in fertility, pregnancy, and infancy may mean significant dangers faced by expecting mothers who choose to use cannabis products.

As always, it is important to consult with your physician and raise any questions or concerns you may have regarding the use of a natural product like CBD.

2-arachidonoylglycerol (2-AG)

Although the 2-AG endocannabinoid doesn’t receive the same praise or attention as amandamide, it has been shown to be present at concentrations 170x greater than anandamide. 2-AG plays a role in governing:

  • Mood
  • Metabolism
  • Immune Function
  • Reproduction
  • Memory
  • Movement
  • Pain
  • Sleep
  • Bone Health

2-AG originates from arachidonic acid, EPA, and DGLA. Great foods to eat to increase the omega-6 building blocks for 2-AG include:

  • Hemp
  • Poultry
  • Pasture Raised Eggs
  • Fish
  • Shellfish
  • Flaxseed

Keep in mind that experts recommend consuming omega-6 fats alongside omega-3 in a 3:1 ratio. Unfortunately, most American diets see a consumption of omegas at a 20:1 ratio!

Anandamide is a selective partial agonist for the CB1 receptor, 2-AG is a full agonist of both the CB1 and CB2 receptors.

While FAAH plays a role in breaking down 2-AG, Monoacylglycerol Lipase (MAGL) metabolizes around 85% of all 2-AG. To date, the only MAGL inhibitor shown to increase 2-AG is JZL184.

However, knowing that 2-AG is the primary cannabinoid with activity at the CB2 receptor, increasing CB2 receptors could be useful.

The probiotics Lactobacillus acidophilus has been shown to increase CB2 receptors in the intestines.

While probiotics are always a good idea, prebiotics are an often overlooked solution to increase the health of our microbiome and the number of CB2 receptors.

Prebiotics are the food source for good bacteria. Food sources that provide a good amount of prebiotics include:

  • Leeks
  • Jerusalem Artichoke
  • Onions
  • Garlic
  • Baobab
  • Leafy Greens
  • Chicory
  • Banana

While THC has a strong binding affinity for both CB1 and CB2, cannabidiol (CBD) has little affinity for either receptor. Instead, CBD exhibits most of its natural benefits through indirect actions (or by activating non-cannabinoid receptors/ion channels) such as:

  • Potentiating Glycine Receptors: Glycine receptors are the most widely distributed inhibitory receptor in the central nervous system, and plays a significant role in pain perception via the spinal cord and brainstem. CBD has been found to potentiate these receptors, generating excitement for its potential use treating chronic pain and inflammation. [S]
  • Binding with the Dopamine D2 Receptor: Many commonly prescribed antipsychotic pharmaceutical drugs target this receptor, and this may help explain CBD’s potential benefit in managing schizophrenia. [S]
  • Enhancing Adenosine Activity: CBD partially prevents the reuptake of adenosine, via inhibition of the equilibrative nucleoside transporter 1 (ENT1). This interaction with adenosine is thought to play a large role in CBD’s potential benefits for inflammation and autoimmune conditions. [S]
  • Fatty Acid Amide Hydrolase (FAAH) Inhibition: This leads to higher levels of endocannabinoids such as anandamide. Endocannabinoids exhibit activity at CB1 and CB2 receptors, providing a myriad of natural benefits. [S]
  • Activating PPAR-gamma Receptors: PPAR-gamma receptors are located on the cell’s nuclei and play a role in degrading beta-amyloid plaque, as well as lipid uptake, insulin sensitivity, and dopamine release. This action explains why CBD may have benefits with regards to diabetes, schizophrenia, and Alzheimer’s. [S]
  • Antagonizing GPR55 Receptors: GPR55 receptors are widely distributed in the brain (especially the cerebellum) and help control bone density and blood pressure. Additionally, GPR55 promotes cancer cell proliferation when activated. These facts may explain CBD’s potential role in assisting with osteoporosis and high blood pressure. [S]
  • Activates the 5-ht1A Receptor (at high doses): The 5-ht1a receptor helps regulate anxiety, addiction, appetite, sleep, pain perception, nausea, and vomiting. CBDA (the raw form of CBD) shows an even higher affinity for this receptor than CBD. [S]
  • Activating TRPV1 Receptors: Involved in regulating pain, body temperature, and inflammation. Other substances targeting TRPV1 receptors include anandamide, AM404 capsaicin, and various cannabinoids such as CBN, CBG, CBC, THCV, and CBDV.
  • Being an Allosteric Modulator: Allosteric modulators change the shape of specific receptors to alter their ability to interact with neurotransmitters fundamentally. CBD is an allosteric modulator of mu and delta opioid, CB1, 5-ht3A, GABA-A, and a7-AChR receptors – owing to a myriad of natural benefits from relief of depression to enhanced memory and learning abilities. [S], [S], [S], [S]

CBD Oil for Endocannabinoid System Health?

Cannabidiol is emerging as a promising natural supplement for a countless number of widespread health concerns, many of which are difficult to treat through allopathic medicine.

If you feel you are experiencing any or all of the symptoms of CECD, or are simply looking to increase your endocannabinoid levels, consider talking to your physician about CBD oil. Use this information as your starting point and do not be afraid to begin a real dialogue.

We know it is a challenge to wade through the medical and scientific information and we hope this gives you the confidence you need to find the best solutions for you and your lifestyle.

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CBD oil has many helpful-- not to mention, natural-- benefits physically and mentally. CBD has been heavily studied to relieve ...
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CBD for Runners

CBD for Runners

If you are an avid runner, you are always looking for safe and healthy ways to improve your performance and ...
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Can you use CBD if you are sober?

Can you use CBD if you are sober?

Can you use CBD if you are sober? Recovery from drug or alcohol addiction isn't just about abstinence. For many, ...
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What Is CBD Wax and How to Use It?

What Is CBD Wax and How to Use It?

If there's anything we've learned from the last few years of incredible development, it's that the cannabis plant can take ...
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CBD Gum: Does it Actually Work?

CBD Gum: Does it Actually Work?

By now, you are probably aware that there are a lot of CBD products on the market that can help ...
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Everything You Need to Know About CBD Oil in Indiana

Everything You Need to Know About CBD Oil in Indiana

If you have never tried CBD oil and you live in Indiana, you probably have a lot of questions. You ...
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CBD and Parenting: Understanding The Best Options For Your Child

CBD and Parenting: Understanding The Best Options For Your Child

CBD (short for cannabidiol) has become an alternative consideration for many parents around the world. Countless families swear by CBD ...
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What You Need to Know About CBD & Birth Control

What You Need to Know About CBD & Birth Control

Birth control remains one of the greatest biomedical advances in the last century, giving women and couples the opportunity to ...
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Complete Guide to CBD Topicals

When shopping for CBD, it's essential to find the best product for your needs and your lifestyle. While CBD tinctures ...
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CBD Edibles vs. Capsules: Which Is Better?

For people who are considering CBD or have already started trying what is available, one of the most common questions ...
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How Does CBD Oil Impact Cellular Function?

CBD oil is well known for its ability to regulate pain and inflammation, making it a valuable tool in the ...
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A Mysterious Syndrome: What Is Cannabinoid Hyperemesis Syndrome (CHS)?

Cannabinoid hyperemesis syndrome (CHS) is a true mystery. It can pop up out of nowhere for chronic cannabis users, and ...
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Industrial Hemp vs. High-CBD Marijuana: What It Means for Your CBD

When you first begin researching CBD oil, it can be hard to understand what you are reading. What exactly is ...
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Can CBD Oil Help Resolve the Opioid Crisis?

Death by overdose has become the largest killer of Americans under the age of 50, and with opioids responsible for ...
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The Complete Guide to Cannabinoids

The most famous cannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is most widely known for its mind-altering, high-inducing properties, ...
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What Is CBG?

Because harvested and dried cannabis or hemp material only contains trace amounts of cannabigerol (CBG), it is often considered to ...
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How Long Does CBD Last?

With cannabidiol (CBD) oil becoming more widely available, it is being sought out by an ever-growing number of people due ...
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CBD Industry Update: First Half of 2019

In 2018, the United States saw exponential growth in CBD oil product development and sales. Halfway through the year, the ...
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What Is THCV?

The cannabis sativa plant contains hundreds of cannabinoids, each one presenting its own unique qualities and potential benefits. You may ...
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What Is CBN?

Cannabinoids have taken over the natural health discussion, and with good reason. Research is continuously finding new ways in which ...
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What is CBC?

One of the lesser-known cannabinoids, cannabichromene (CBC) may be able to do some pretty incredible things. Recent scientific study has ...
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What Is THCA?

Learning about the phytocannabinoids that exist in the cannabis plant family can feel a little bit like sifting through alphabet ...
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Can You Use CBD Oil While Pregnant?

Cannabidiol (CBD), is becoming widely used for its reported therapeutic benefits, which include pain reduction, nausea relief, and mood elevation ...
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an illustration of Tetrahydrocannabinol's (THC) molecular structure

What is THC?

Tetrahydrocannabinol (THC) is probably the best-known cannabinoid found in the cannabis plant. THC is the psychoactive, intoxicating, and mind-altering compound ...
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an illustration of CBDA's (cannabidiolic acid) molecular structure

The Many Potential Benefits of Cannabidiolic Acid (CBDA)

Of the many phytocannabinoids found in cannabis plants, tetrahydrocannabinol (THC) and cannabidiol (CBD) are likely the most well-known.  That's why ...
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Plant-Based Medicine vs. Big Pharma: What It Means for Your CBD Oil

The role of “Big Pharma” in healthcare is a contentious subject and one that’s working its way into discussions around ...
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Combining Essential Oils with CBD Oil: Maximizing the Benefits

With more and more research coming out that shines a light on the reported health benefits of CBD and essential ...
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Can You Build a Tolerance to CBD?

Researchers are finding that CBD oil may be able to treat the symptoms of a whole host of diseases and ...
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Is Potent Better When It Comes to CBD Oil?

When you first decide to use CBD oil, it can be hard to know where to start. With so many ...
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Dietary Supplements and CBD Oil: All You Need to Know from Vitamin A to Zinc

Health supplements are becoming increasingly commonplace as average Americans struggle to meet their recommended daily intake of vitamins and minerals ...
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Terpenes in CBD Oil: Why are they important?

If you've spent any time reading about CBD oil and cannabis lately, it is likely you've seen terpenes mentioned more ...
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Is CBD Oil Legal in My State?

If you’re interested in purchasing CBD oil but aren’t sure if it’s legal in your state, you’ve come to the ...
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Buying Hemp Oil on Amazon: What You Should Know

The CBD oil industry is one of the fastest-growing in North America and as such, it should come as no ...
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Endocannabinoid Production in the Human Body

Not long after the first cannabinoid was isolated from the cannabis plant, scientists discovered the human body produces similar substances ...
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Cannabis in Canada: The Status of CBD Oil

Those friendly neighbors on the northern U.S. border have a reputation for being fairly liberal minded. In fact, as of ...
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Your Guide to CBD Vape Oils and CBD Vapes

As people continue to abandon cigarettes, vaping is becoming increasingly popular. And, as the range of vape oils, vape juices, ...
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7 Tips for Buying CBD Products

Ready to make your first CBD oil purchase but aren’t sure where to start? Well, you’ve come to the right ...
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Guide to CBD Vape Juice, Vape Oil, and E-Liquid

With so many CBD oil products and delivery formats available for purchase, knowing which one is right for you can ...
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CBD Flower: Everything You Need to Know

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Everything You Need to Know About CBD Oil Drops

CBD oil drops are one of the most popular ways to take cannabidiol (CBD). They are a cost-effective and convenient ...
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A Comprehensive Guide to CBD Tinctures

If you’re new to the world of CBD oil, there’s a lot of new terminology to take in; one term ...
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CBD Gummies 101

Is there nothing cannabidiol can’t do? The wonder compound—more commonly known as CBD—has been hailed as everything from a digestive ...
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The Athlete’s Guide to CBD

As an athlete, the less time you can spend doing online research, the more time you can devote to your ...
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CBD Oil Microdosing: Everything You Need to Know

CBD oil microdosing is a concept that gets thrown around a lot these days, but what does it actually mean? ...
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CBD Oil for Tattoos: Pain, Nerves, and Aftercare

Because CBD oil has also been shown to reduce inflammation and swelling while promoting cell reparation, CBD topicals (e.g. balms, ...
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CBD Oil vs. Hemp Oil: What’s the difference?

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Does CBD Oil Have Any Known Side Effects?

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Beginner’s Guide to CBD Oil: How to Take CBD

Beginner’s Guide to CBD Oil: How to Take CBD

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What’s the Difference? CBD Isolate vs. Full-Spectrum CBD Oil

There are two main types of cannabidiol (CBD) extract utilized by vendors - purified, crystalline isolate, often labeled as ‘CBD ...
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Is CBD Oil Safe for Children?

With frequent news reports about newly discovered uses for cannabidiol (CBD) in healthcare, a number of parents are investigating its ...
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The Women’s Guide to CBD Oil

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Does CBD Oil Affect Your Hormones?

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Is CBD a Schedule 1 Drug?

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Can CBD Oil Help Build Muscle?

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Should You Add CBD Oil to Your Post-Workout Recovery Routine?

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Can CBD Oil Improve Memory?

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Should You Mix CBD Oil and Caffeine?

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How to Talk to Your Doctor About CBD Oil

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CBD Oil in Skin Care Products: Does It Really Make a Difference?

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Can You Use CBD Oil While Breastfeeding?

As a breastfeeding mother, you know how carefully you need to monitor your consumption. Certain foods and drinks are off ...
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CBD Oil Extraction Technique – Ethanol vs. Supercritical CO2

There are several techniques available for extracting CBD oil from the cannabis plant. The two most common are ethanol extraction ...
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What is CBD Shatter?

CBD shatter is one of the purest forms of cannabidiol (CBD oil) that money can buy and it is completely ...
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Can CBD Oil Get You High?

One of the first questions asked by people just learning about CBD oil is, “Can CBD oil get you high?” ...
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CBD Oil and Fertility: What You Need To Know

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6 Smart Questions to Ask BEFORE You Buy CBD

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One response to “The Endocannabinoid System – What You Should Know”

  1. Avatar Linda S Reinhard says:

    I have severe chronic pain in my right shoulder and arm, lower back pain I also have stomach problems pelvic problems Doctors can’t find anything wrong, x-rays, MRI of the spine and MRI of the brain, seen a gastroenterologist which nothing found wrong. But I have severe chronic pain, will CBD help me? I’m not living, just surviving. Please let me know.Thanks

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