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Working Together: Cannabidiol and Our Endo-Cannabinoid System

The endo-cannabinoid system (ECS) is our body’s own, natural, internal structure which both produces, and receives the effects of, endogenous cannabinoids. CBD is a phyto-cannabinoid, that works directly upon our endo-cannbinoid system. Say what??? Well, we find the language a little obtuse as well… Endogenous Cannabinoids: We Make Them! ‘Endogenous’ (or ‘endo’) is defined as […]

CB1, an endogenous cannabinoid receptor, is the most abundant receptor in our central nervous system. CBD binds directly to this receptor.

The endo-cannabinoid system (ECS) is our body’s own, natural, internal structure which both produces, and receives the effects of, endogenous cannabinoids. CBD is a phyto-cannabinoid, that works directly upon our endo-cannbinoid system. Say what??? Well, we find the language a little obtuse as well…

Endogenous Cannabinoids: We Make Them!

‘Endogenous’ (or ‘endo’) is defined as the ‘substances which originate from within an organism’. Thus ‘endo-cannabinoids’ are cannabinoids that our bodies make that are similar (if not the same, in many instances) to the more than 60 known cannabinoids produced by the Cannabis sativa plant.

So we produce our own cannabinoids, which bind to receptors throughout our body. The CB1 – or the ‘first cannabinoid receptor’ discovered by science – is in fact THE most abundant receptor found in the Central Nervous System.

Phyto-Cannabinoids: Those Made by Cannabis sativa

‘Phyto-‘ cannabinoids produced by Cannabis are similar in molecular structure to those produced by our bodies (two thus far have been found to be exactly the same, and the research has truly just begun). Phyto-cannabinoids interact with receptors in our central nervous system and throughout the body, producing a wide variety of effects. However, the non-psychoactive CBD doesn’t seem to bind strongly to our own cannabinoid receptors, but acts in a different way…

THC & CBD: The Most Well-Researched Phyto-Cannabinoids

There is a difference…CBD is extracted from 100% legal industrial hemp, organically grown in Europe, a truly different plant strain than Cannabis sativa grown for its THC. Our raw CO2 extract contains an abundance of CBD.

With the well-known psycho-activity of delta-9-tetrahydrocannabinol (THC), the use of cannabis all-day, every-day, even for health support, has some obvious limitations.
While the science supporting THC for medicinal applications is growing quickly, in most cases, no matter what health-supportive purpose one is using cannabinoids for, being ‘high’ all day won’t work for most of us.

THC and CBD Molecular Structures Are Very Similar, Yet Their Effects Are Very Different.

However, cannabis has at least 60 other cannabinoids that interact with our endo-cannabinoid system – the most extensively studied of these being CBD.

CBD is the most abundant cannabinoid in the hemp plant, which is virtually free of psychoactive cannabinoids.

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CBD: What We Don’t Know About This Phyto-Cannabinoid

It is important to note that most research illustrating the positive effects of CBD still incorporate only theories for the biochemical mechanism(s) of how CBD actually works. We know it produces particular results in scientific research, but we’re really not sure exactly how it does it.

At the same time, all information included here about how CBD interacts with the endo-cannabinoid system (ECS) are hypotheses which have strong supporting evidence, and are generally accepted by the scientific community.

CBD: What Do We Know?

CBD is recognized with a safe clinical profile, and thus an attractive candidate for therapeutic use (2).  It doesn’t appear that it can be harmful in any way, only that how much one should use for a desired outcome is, as of yet, a scientific unknown.

The challenge in understanding dosages for therapeutically-desired activities is due to a number of factors. It is clear that there is more than one mechanism involved in CBD’s actions, which depends both on the effects being measured and the dosing regime utilized in the experimental conditions (3).

It is also apparent that CBD does not directly activate (technically ‘agonize’) CB1 endogenous cannabinoid receptors. Instead, when it binds to them, it changes our anandamide metabolism by either increasing or decreasing its activity. Anandamide is an endogenous cannabinoid – one made by our own bodies – sometimes referred to as ‘the bliss molecule. (3) ‘Ananda’ is the Sanskrit term for the unbounded happiness of spiritual bliss.

CBD, Anandamide, Mood and Stress

Because CBD has been recognized as a non-psychoactive yet physiologically active, there is a lot of research with regards to its effects related to mood disorders, mental disorders, and brain function.

The ‘Bliss’ Chemical, Our Endogenous Cannabinoid Modulated by CBD.

Individuals can use CBD without getting “high”, still function day to day at work, operate machinery (such as a car), and not become hindered from any activity due to intoxication.

Many human studies have shown that CBD moderates anandamide levels in the body when binding to the CB1 receptor (2). It appears that CBD may lead to homeostasis (‘ideal’ metabolic balance) of anandamide by either up-regulating or down-regulating the activity of FAAH, the enzyme responsible for breaking down anandamide.

By stopping the breakdown of anandamide, endogenous anandamide levels naturally increase; conversely, anandamide levels may decrease with a corresponding increase in FAAH activity.

For example: Anandamide has been shown to be at low levels in psychotic patients (such as those afflicted with schizophrenia). With CBD administration, anandamide levels increase through inhibition of FAAH, and anandamide’s ‘signal strength’ is also enhanced, alleviating psychotic symptoms seen in these patients (1). Interestingly, CBD has also been shown to decrease psychotic symptoms that are a result of THC use (1).

CBD, PTSD and Anxiety

CBD has also shown time and time again its ability to alleviate anxiety, including decrease defensive behaviors, panic attacks, OCD, and post-traumatic stress disorder (PTSD) (3). It has been agreed that CBD possesses anti-anxiety effects, even in healthy volunteers after a simulated public-speaking study (3), and thus even healthy individuals with non “serious” mental disease or ailments can benefit from CBD use.

Based on neuro-imaging studies, CBD changes the activity of brain regions related to controlling emotions by increasing oxygen in the amygdala and the anterior and posterior cingulate cortex (3).

At the same time CBD, through its interaction with the Endo-Cannabinoid System, is able to activate or modify the function of several other receptors and neurotransmitters in the central nervous system (3). It has been well established that cannabinoids in general (and CBD in particular) affect both GABAnergic and dopaminergic pathways. Activation of the GABAnergic system is generally related to calming and relaxation, and activation of the dopaminergic system related to positive, energetic outlook.

CBD and our Endo-Cannabinoid System In a Nutshell

In summary, due to the structure of CBD, it binds to receptors of our own endo-cannabinoid system that are abundant in all of our tissues, especially the brain and spinal cord. Binding of CBD to CB1 & 2 receptors appears in the research to address mood disorders and offer potential support of many conditions, even in otherwise healthy individuals. The primary actions appear to be through the modulation anandamide levels (one of our endogenous canabinoids), and promoting blood oxygen to the brain and acting on various neurotransmitter pathways without getting one “high.”


1. FM Leweke, D Piomelli, F Pahlisch, D Muhl, C W Gerth, C Hoyer, J Klosterkotter, M Hellmich, and D Koethe. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar; 2(3): e94 Link

2. Stephen D Skaper and Vincenzo Di Marzo. endo-cannabinoids in Nervous System Health and Disease: The Big Picture in a Nutshell. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5; 367(1607): 3193–3200 Link:

3. Alline Cristina Campos, Fabricio Araujo Moreira, Felipe Villela Gomes, Elaine Aparecida Del Bel, and Francisco Silveira Guimaraes. Multiple Mechanisms Involved in the Large-Spectrum Therapeutic Potential of Cannabidiol in Pyschiatric Disorders. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5; 367(1607): 3364–3378 Link:

4.  Wolf SA, Bick-Sander A, Fabel K, Leal-Galicia P, Tauber S, Ramierz-Rodriguez G, Muller A, Melnick A, Waltinger TP, Ullrich O, Kempermann G. Cannabinoid Receptor CB1 Mediates Baseline and Activity-Induced Survival of New Neurons in Adult Hippocampal Neurogenesis. Cell Commun Signal. 2010 Jun 17;8:12 Link:

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