Core Cannabis Course: THCP

Welcome to homework assignment CCC 1.17 of the Core Cannabis Course from Higher Learning LV. This assignment teaches students about the recently discovered cannabinoid THCP. This cannabinoid is a chemical cousin of delta-9 and delta-8 THC, but features some unique characteristics that make it worthy of our study and inclusion in the top 25 cannabinoids.

When you complete this assignment, simply click the link at the bottom of the article to return to the master page for this course.

Tetrahydrocannabiphorol (THCP) was discovered only as recently as December 2019 when a group of Italian researchers published a peer-reviewed research study entitled "A Novel Phytocannabinoid Isolated From Cannabis Sativa L. with Cannabimimetic Activity Higher Than Tetrahydrocannabinol: Tetrahydrocannabiphorol."

THCP molecule

One of the most significant results of this research about the new phoral family of cannabinoids is the fact that TCHP features a binding affinity with the CB1 cellular receptor of the endocannabinoid system (ECS) that is 33 times greater than that of its chemical cousin delta-9 THC and a whopping 63 times greater than that of its varin analog cousin THCV.

"THCP was shown to feature a CB1 receptor binding affinity that is 33 times greater than that of THC and 63 times greater than that of its varin analog THCV."

Interestingly, the enhanced molecular binding affinity displayed by this newly discovered cannabinoid led the researchers to theorize that THCP, not THC, may be the source of psychoactivity in certain cultivars of cannabis. "In cannabis varieties where THC is present in very low concentrations, then we can think that the presence of another, more active, cannabinoid can explain [the psychoactive] effects."

THCP biosynthetic pathway
 

The very recent discovery of the THCP cannabinoid means that no meaningful studies have been conducted as follow-on research to the 2019 Italian investigation that identified this cannabinoid. Below, the most important excerpts from the Discussion section of the 2019 study are provided.

"As the pharmacological activity of Δ9-THC is particularly ascribed to its affinity for CB1 receptors, the literature suggests that the latter can be increased by elongating the alkyl side chain, which represents the main cannabinoid pharmacophoric driving force.

"The cutting-edge technological platform of the Orbitrap mass spectrometry can enable the discovery and identification of new compounds."

"Therefore, taking THC as the lead compound, a series of cannabinoids have been chemically synthesized, with their biological potency several times higher than Δ9-THC. To the best of our knowledge, naturally occurring cannabinoids with a linear alkyl side chain longer than five terms have never been detected or even putatively identified in the cannabis plant.

"However, the cutting-edge technological platform of the Orbitrap mass spectrometry and the use of advanced analytical techniques like metabolomics can enable the discovery and identification of new compounds with a high degree of confidence even when present in traces in complex matrices. The biological results obtained in the in vitro binding assay indicated an affinity for CB1 receptors that is more than thirty-fold higher compared to the one reported for Δ9-THC in the literature.

"In particular, Δ9-THCP proved to be as active as Δ9-THC, but at lower doses. In fact, the minimum THC dose used in this kind of test is 10 mg/kg, whereas Δ9-THCP resulted active at 5 mg/kg in three of the four tetrad tests.

"Δ9-THCP proved to be as active as Δ9-THC, but at lower doses."

"These results, accompanied by the docking data, are in line with the extensive structure-activity relationship (SAR) studies performed through the years on synthetic cannabinoids, revealing the importance of the length of the alkyl chain in position 3...in modulating its...affinity with CB1 receptors.

"Although the amount of the heptyl homologues of CBD and Δ9-THC in the FM2 variety could appear trifling, both in vitro and in vivo preliminary studies reported herein on Δ9-THCP showed a cannabimimetic activity several times higher than its pentyl homolog Δ9-THC.

"Moreover, it is reasonable to suppose that other cannabis varieties may contain even higher percentages of Δ9-THCP. It is also important to point out that there exists an astonishing variability of subject response to a cannabis-based therapy—even with an equal Δ9-THC dose. It is therefore possible that the psychotropic effects are due to other extremely active phytocannabinoids such as Δ9-THCP.

"We believe that the discovery of an extremely potent THC-like phytocannabinoid may shed light on several pharmacological effects not ascribable solely to Δ9-THC."

"However, up to now nobody has ever searched for this potent phytocannabinoid in medicinal cannabis varieties. In our opinion, this compound should be included in the list of the main phytocannabinoids to be determined for a correct evaluation of the pharmacological effect of the cannabis extracts administered to patients. In fact, we believe that the discovery of an extremely potent THC-like phytocannabinoid may shed light on several pharmacological effects not ascribable solely to Δ9-THC.

View the original study.

The novel nature of THCP means that products featuring it and cannabis and hemp cultivars featuring meaningful volumes of it have yet to emerge in either the legal or underground cannabis markets in the United States.