Word of a new form of THC (THCP) hit the mainstream media last month and exploded into frenzied hoopla that a cannabinoid 30-times stronger than anything seen before was coming to the market. While there was indeed a new cannabinoid discovered by Italian scientists, with a stronger affinity for binding to the receptors of the brain, there is so much more to the story about this initial finding. So we reached out to Ben Armstrong with Juniper Analytics to help us sift through the report and understand the science behind this study. It is of note that Ben has read the paper, and knows the background science of isolating cannabinoids for research, but did not directly conduct this research. However, he did offer some insight into what this new information means.
The Structure of a THC Molecule, THCP
First, we begin with a little background on the study submitted by an Italian research group with members from the National Council of Research, among other groups. The most interesting finding- that has everyone buzzing is the discovery of a new form of THC—dubbed Delta-9 THCP— a phytocannabinoid with a 7-chain carbon atom tail and its influences on biological activity. Up to this point, scientists thought only cannabinoids with a 5-atom chain were naturally occurring.
Ben explained that essentially THCP mimics the same molecular properties as Delta-9 THC, but the extended tail gives the molecule a greater affinity for bonding with the CB1 and CB2 receptors. However, binding with more affinity does not mean the molecule causes stronger effects.
THC molecule, U.S. Institute of Medicine, March 1999
On the right side of the currently known THC molecule there is a crooked tail with five points after the rings, each one representing a carbon atom. The hypothesis is that THCP, with seven carbons, will bind much more tightly (with a greater affinity) than the one with only five carbons. The term binding affinity is widely used in molecular sciences—particularly to define the potency of drugs—as a description of anything that binds to a brain receptor giving scientists a unit of measurement for the prevalence of attraction between the two. Ben urges that this term takes into account many more factors than just how strong the molecule connects to the brain.
“Theoretically, the more affinity, the smaller amount of medication needed to solicit effects, but we don’t know if that’s the case here,” he said.
That is precisely the rabbit hole that many in the media are going down to claim that this could be a much stronger THC, but we don’t necessarily know that. According to Ben, all we know is that it bonds better. While a striking discovery, this doesn’t necessarily indicate that someone would get a 30x more intense psychotropic effect (what recreational consumers would call “The High”) in the brain.
What takes place within that bond is not something that Ben is an expert on, and something that scientists are still studying to figure out. Researchers have identified nearly 150 different cannabinoids, each having its own binding affinity. Many cannabinoids have known psychoactive effects, in that they bind to a receptor, but not necessarily a psychotropic effect that induces a high, which is why it’s great to see a group on the other side of the world putting time and resources into finding these answers.
“What those affinities are and how they influence the downstream effects is not super well known at this point,” he said. “A respected journal getting a lot of media attention on cannabis is how we are going to answer these questions as to what cannabinoids are out there, how they bind to these receptors, and whether they elicit psychoactive versus psychotropic effects.”
How Scientists Isolated this New Compound
According to the paper, scientists took an ethanol extract of the strain FM2 provided by the Italian Military Chemical Pharmaceutical Institute and put it in a liquid chromatography system coupled to a high-resolution Orbitrap Mass Spectrometer, which for people familiar with the science means they used this system to separate and analyze the extract.
Not a chemistry expert? Ben put it this way: Say you have a bag of Skittles with all the colors of the rainbow and you want to study the molecules of the green ones versus the red. This machine is going to separate those little candies based on color, diluting the green ones first, then the red, then the orange ones so you have them all divided out by color. Then the high-resolution Mass Spec uses extremely complicated chemistry to look at what the molecules are composed of, and what parts show up in the fragmentation patterns, by blasting everything apart to differentiate that the green Skittle has this stuff going on and the red Skittle has that other stuff happening. Scientists involved in this study were able to show precursor ions for THCP, fragments that had not been identified in other cannabinoids previously.
Specific Physical Effects
Some members of the cannabis industry speculate that this could be the start of isolating cannabinoids for specific physical effects, but that’s a slippery slope, says Ben. He doesn’t necessarily disagree with the statement, but we don’t know for sure at this point where this information will lead. People are already extracting cannabinoids for specific uses, as seen in the hemp industry with CBD extracts. With exceptional techniques, one could isolate THCP from the other cannabinoids, but that shrinks the full picture of what cannabis molecules can do collectively.
“There are now well over 100 identified cannabinoids, and people should be interested in talking about the Entourage Effect that comes from the combination of these compounds,” Ben said. “There are a lot of important interactions that take place between the cannabinoids, terpenes, and other compounds in cannabis all working synergistically to elicit molecular effects in the body.”
What Happens Next
Above all, Ben says this certainly begs the question as to whether THCP is present in other strains beyond just the one tested in Italy.
“If I had to guess THCP is in many varieties out there and it could help to explain some of the psychotropic effects people get from strains that may not be attributed to just the level of THC,” he said. “Is Delta-9 THCP present in other cultivars of cannabis that we see on a regular basis here in Oregon, California, or Washington? If not, why? If so, how?”
Ben believes one of the next steps should be comparing this Delta-9 THCP to traditional THC for its dose-dependent effects.
“How do you measure someone’s high? You need a metric. In the paper, they use locomotion, meaning if you’re high you’re not going to move around as much,” he said. “It would be interesting to look at the effects of THCP versus Delta-9 THC. That would at least tell us if they see 30-times greater hypo-locomotion or other events in the test subject.”
What’s Really The Big Deal Here?
Of course, it’s exciting to see a new naturally occurring cannabinoid identified, but Ben thinks there is a more significant win here.
“This finding is a big deal to me and others in the industry because it shows there are academic groups around the world working on isolating and understanding the in-vitro and in-vivo activity that cannabinoids and other molecules in cannabis contain,” he said. “A lot of us have hoped for these studies because we’re decades behind in the molecular understanding of cannabis.”
Scientists have conducted reputable research studies for tons of plants, pharmaceuticals, and other medicinal compounds, so to see groups start to take on these questions about cannabis is the crucial part that all of us should take out of this study.
“It’s exciting to see a major scientific research report on cannabinoids in a top academic journal that has been peer-reviewed and accepted by a group of experts in molecular biology,” Ben concluded. “Researchers will not make this claim lightly, which holds a level of authority over people writing whatever they want and posting it to Google.”
You May Have Missed: