Previously in Puff Puff Pass: The Tale of THC, we discussed the journey that d9-Tetrahydrocannabinol (THC) takes as it traverses our bodies, and into our brains. We learned that the chemical mechanism that gives us our “high” is produced as a result of THC binding to Cannabinoid Receptor-1 (CB-1).

Many wonder if the second most recognizable cannabinoid, cannabidiol (CBD) will also get you high.

In short, the answer is no, but surely you would like to know why!

Often when we crack open a cold bag of buds, we take for granted that we are about to perform a chemistry experiment. Every minute detail of the structure of THC—from how it behaves around water (hydrophobicity), to its electrostatics (distribution of positive and negative charges)—determines how tightly it will bind to its target, CB-1 (Figure 1).

Though there are minor differences between THC and CBD, the later’s bond with CB-1 is remarkably looser than it’s cousin, THC, by 3-5 fold.

Figure 1. Despite minor stylistic differences, the only true chemical differences are in the highlighted regions. This break in the ring structure from THC to CBD allows CBD more flexibility, and the additional hydrogen (H) on the oxygen (O) allows for an additional type of bond (hydrogen bond). The additional hydrogen bond, and addition of the double bond (circled in red) are examples of differences in charge distribution, as discussed above. Structures pulled from Google image search of THC and CBD respectively.

You might think that despite its weaker attraction to CB-1, CBD would still cause a similar effect as it is still moderately bound, but you’d be mistaken.

In fact, CBD is observed to have an opposite affect on CB-1 than THC.

There are a few perspectives that we must observe to get even a sliver of the story. Biochemistry does a stupendous job of being exceedingly complex!

The first perspective comes from the structure of CBD, which, as stated previously, is different from THC in its specific shape and distribution of charge. These differences, no matter how minute, can have drastically different effects on CB-1.

Now, let us look at the perspective of the receptor itself.

You may recall CB-1, a structure which was only recently determined, belongs to a class of receptor/signaling proteins known as G-protein coupled receptors (GPCRs). There are entire textbooks dedicated to these proteins, so I will give you the quick and dirty.

The helices that permeate through the cellular membrane are very dynamic, and their movements are determined by the molecule that binds to it (i.e. THC or CBD), and they are extremely sensitive.

Despite the striking similarities between THC and CBD, the differences are distinct enough to have differential effects on these sensitive helices; moving in such a way to elicit opposing effects. Though these effects may seem minor, this type a receptor results in large multiplicative signaling cascades within cells.

Remember how I said biochemistry is exceedingly complex? We only observed one interaction, setting aside the myriad of resulting chemical reactions inside the cell. Furthermore, differences in how they affect our consciousness occur on a larger scale—more biology than chemistry if you will!

Though these atomic interactions are seemingly insignificant, they cannot be taken for granted when observing biology. After all, biology is an intimate, intricate, intertwining of physics, mathematics and of course, chemistry.

RELATED: 10 Little-Known Uses for CBD
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