THC, THCV, THCB, THCP, c’mon! You gotta be making this up right?!? As cannabis legalization has started in states all across the country, it has led to an explosion of cannabis knowledge and information. Far from the days of THC (Δ9-tetrahydrocannabinol) is the thing in cannabis that gets you high, there are now a huge variety of cannabinoids found on the market and being discussed in social media. Oftentimes the nomenclature used for these is quite confusing to anyone that hasn’t delved deep into the subject. It doesn’t help that the library of cannabinoids being identified is constantly expanding.
The newest rage these days is THCP (tetrahydrocannabiphorol) which has been found to be more potent than THC! This is in contrast to THCB (tetrahydrocannabutol) which was discovered last year and found to have cannabinoid receptor binding affinities much closer to that of THC. You may have also heard about THCV (tetrahydrocannabivarian), which started to gain traction in the news a few years back. So what gives? What is the difference between all of these different THC type cannabinoids? There’s a bit of good news, and then a bit more good news involved in answering that question. The good news is that the difference is actually pretty easy to understand, and the more good news is that in order to really understand it, we get to talk a little chemistry!
When we look at the chemical structures of THC, THCV, THCB and THCP, we see that they are all mostly the same, with the exception of what is called the alkyl side chain. This portion is called the alkyl side chain because it is made up of only carbon and hydrogen atoms where each of the carbons is connected to a total of four different atoms through single bonds. In ordering the molecules by side chain length, we see that THCV has three carbons and seven hydrogens, THCB has four carbons and nine hydrogens, THC has five carbons and eleven hydrogens and THCP has seven carbons and fifteen hydrogens. So the only real difference between any of these compounds is the length of this alkyl side chain.
So how does this affect binding you might ask… well, that has to do with the interactions with the cannabinoid receptors. The carbon-hydrogen bonds in the alkyl side chains allow for interactions with carbon-hydrogen bonds on the receptors. While these interactions are only part of what causes the entire molecule to bind to the receptor, since the rest of the molecule is the same for all of these THC type compounds, we can focus on the interactions directly related to the alkyl side chain. The cannabinoid receptor has a binding pocket on it that is made of amino acids which contain carbon-hydrogen bonds as well. The alkyl side chain on all of the THC type cannabinoids will fit into this pocket. However, since they all have different lengths, some fill this pocket better than others.
This means that molecules like THCV and THCB don’t quite fill up the binding pocket as much as THC. On the other side of this, the newly discovered THCP fills this binding pocket even better. This allows for an increase in the number of interactions between the alkyl side chain of THCP with the binding pocket of the receptor. The increase of interactions then leads to stronger binding within this pocket, thereby causing the THCP to “stick” a bit better than THC. The small differences between these compounds such as one or two carbons and hydrogens here and there is what explains the wide range of cannabinoids made by the cannabis plant, with around 150 cannabinoids already being discovered.
An astute observer however, might have noticed that while I’ve been throwing around all of these different THC type cannabinoids, I have yet to mention THCA (tetrahydrocannabinolic acid). The difference between THCA and the other THC type compounds we’ve discussed so far isn’t based on the length of the carbon hydrogen side chain. The difference between THCA and THC is a carboxylic acid group that is on THCA but gets lost in the conversion to THC, a process called decarboxylation. The plant actually makes the acidic form of the cannabinoids and through heat or light exposure, a molecule of CO2 gets lost creating the non acidic form of the cannabinoid. This means that just as THC has an acidic version THCA, the other THC type cannabinoids, when made by the plant, also have their acidic versions. Note though that these compounds can also be synthesized in a lab by processes not going through the acidic forms.
I have also so far only discussed the THCP compound recently discovered in cannabis. This discovery also included the discovery of CBDP (cannabidiphorol), which is related to CBD (cannabidiol) in the same way that THC is related to THCP, the extending of the alkyl side chain by two carbon atoms.
The importance of the similarities between these different compounds is in allowing for a systematic catalog of cannabinoids to be developed. Using the similarities between these compounds it is easier to digest the vast array of total cannabinoid compounds. Understanding what THC type and CBD type cannabinoids are, allows for an easier understanding of the differences that occur in the cannabinoid world. The cannabis plant is giving off a vast array of useful biological compounds that can be utilized in a number of different ways. Increasing this systematic knowledge base of cannabinoid types opens up vast possibilities.
As such, let us take a minute to applaud the work of so many hardworking scientists that continue to push our current understanding of the cannabis plant as well as it’s interactions with our own endocannabinoid system and other numerous biological targets! The devils in the details, and there are a lot of details! Kudos to the researchers who persist through it all to expand our knowledge of our shared passion… Cannabis!!