One of the most celebrated elements found in cannabis is a chemical called CBD which is short for cannabidiol. It is a non-psychoactive compound that is a powerful anti-inflammatory, anti-spasmodic, and anti-seizure medication. Yet, its list of accolades doesn’t end there.

So far, the endocannabinoid system (meaning endogenous cannabinoid) is the largest receptor system known to exist in the human body. It’s a system that helps to maintain homeostasis, to keep things running in tip-top shape. That means that we already have our own versions of pot molecules in our nervous systems.

That alone is extremely interesting. It accompanies a growing list of psychoactive elements found in our brains such as PCP, DMT, opiate, and Valium-like molecules among others. The correlation of human neurotransmitters with plant molecules is perhaps one of the most baffling, yet intriguing, discoveries ever made. Now we can add endocannabinoid molecules acting as neurotransmitters in our brains and peripheral nerves.

Let’s examine just how this interesting little molecule exerts its effects. The endocannabinoid system so far has two known receptors, the CB 1 & 2, with a possible third candidate the GPR55 receptor system. CB 1 is mostly found in the brain while CB 2 is in the peripheral nervous system. CBD has a complicated portfolio of direct and indirect actions both centrally and in peripheral nerves.

We now know that CBD acts as a weak antagonist (it blocks the receptor) on CB 1. Recently it was revealed that CBD has a stronger antagonist effect on CB 2 within the endocannabinoid system in humans.

Classically, CBD antagonizes these receptors but it indirectly stimulates endogenous cannabinoid signaling by suppressing fatty acid amide hydroxylase (FAAH), which is the enzyme that metabolizes anandamide.

Anandamide is an endogenous cannabinoid that activates the CB1 receptor. CBD therefore, indirectly leads to increased CB1 signaling through increasing the quantity of anandamide at the receptor in spite of the fact that CBD weakly antagonizes CB1. The end result may be to stimulate the system. Stimulating CB 1 is where the “high” from pot smoking comes from. Incidentally, CBD in excess quantities, may decrease the high from THC since it is an antagonist of CB1.

But wait there’s more to it. CBD also stimulates the release of 2-AG another endogenous cannabinoid which stimulates both CB1 and CB2 receptors. In the final analysis the effects are a complicated symphony of stimulation and suppression leading to the classic experience of smoking or ingesting marijuana, or to the pain relieving effects of ingesting CBD preparations.

Looking at the figure below we see that CBD also acts as an agonist at the 5HT1a receptor (the serotonin receptor where LSD works), and an agonist at the vanilloid receptor known as TRPV-1.
Lastly, it also stimulates adenosine receptors. One of which acts as a powerful anti-inflammatory known as A2A. Don’t forget that CBD is a potent antioxidant in its own right. The ability of CBD to quench free radicals is more powerful than vitamin C or E. Free radicals have been implicated in dozens of disorders including the aging process itself. If we combine CBD with THC we see even greater antioxidant effects[ref]CBD: How It Works. Martin A. Lee. (PDF O’Shaughnessy’s Autumn 2011)[/ref].

CBD table
Figure 1 CBD How it works from Martin A Lee (O’Shaughnessy’s • Autumn 2011)

As you can see from the above table there are six systems where we know CBD acts. It stimulates serotonin, vanilloid and adenosine receptors leading to possible applications in treating depression, insomnia and appetite (serotonin); reducing pain and inflammation (vanilloid); and in the treatment of cardiovascular disorders (adenosine) respectively. By antagonizing (blocking) the GPR55 system possible applications are in the treatment of osteoporosis, high blood pressure, and cancer metastasis especially with breast cancer.

Lastly, during myocardial ischemia the heart often times misbehaves and can develop serious rhythm disturbances such as ventricular tachycardia (V-tach). In a rat model CBD was shown to decrease the incidence of V-tach during coronary artery occlusion[ref]British Society for Cardiovascular Research doi:10.1136/heartjnl-2011-301156.17 Y Hepburn, K Walsh, L Wainwright. The Robert Gordon University, School of Pharmacy and Life Sciences, Aberdeen, UK; (web: 11/24/2014[/ref] but just how it does that remains a mystery.

There is still much needed work to be done before we’ll have it clear as to the role of cannabinoids in treating the numerous expressions of inflammatory diseases. To do that we’ll need to get pot removed from its current schedule I status to at least schedule II so that research dollars can pour into the system.

Finally, let’s take the trillions wasted in drug interdiction and the prison system for non-violent drug offenders toward research into cannabinoids. If we do that you got yourself a “Going Jesse.” It only makes one wonder what bounty might already be available to our moribund masses had President Nixon or Carter legalized marijuana back when they should have.
Regardless of where the chips finally fall there’s much promise in the years to follow.