A new phytocannabinoid isolated from Cannabis sativa L with a cannabimimetic activity 30 times greater than THC has been detected in cannabis
The world's most powerful vegetable cannabinoid Tetrahydrocannabiphorol (THCP) was recently discovered in a study in Italy. It is almost identical in structure to THC but is 33 times stronger than it, as well as CBDP, the corresponding derivative of CBD. Research could lead to the development of much more potent THCP strains in the future.
So far, almost 150 phytocannabinoids have been detected in the cannabis plant, although most of them have not been isolated or characterized. CBD and Δ 9 -THC well known have been widely characterized and have been shown to have interesting pharmacological profiles, hence the attention paid to the biological activity of their known counterparts such as CBDV and Δ 9.–THCV has recently increased.
Other counterparts like those belonging to the orcinoid series are hardly studied, probably due to their very small quantity in the plant, which makes their isolation very difficult. In recent years, research in agricultural genetics has made great strides in the selection of rare strains that produce large quantities of CBDV, CBG and Δ 9 -THCV, it would therefore not be surprising to see in the near future varieties of cannabis rich in other minor phytocannabinoids. This genetic selection would make it possible to produce extracts rich in a specific phytocannabinoid with a characteristic pharmacological profile. For this reason, it is important to perform a complete chemical profiling of a variety of medicinal cannabis and an in-depth investigation into the pharmacological activity of minor and lesser known phytocannabinoids.
The new cannabinoid, whose full name is Tetra-Hydro-Cannabiphorol (Tetra-Hydro-Cannabiporol), was first able to completely isolate from plant extraction, as well as to characterize and produce it artificially.
The most promising discovery about THCP is that it has a significantly higher ability to bind to cannabinoid receptors than even THC itself, especially the CB1 receptor.
In the study, published in the scientific journal Nature, the researchers hypothesize that the cannabinoid THCP could be one of the factors responsible for the characteristics of different varieties of cannabis even when they contain the same concentrations of THC and CBD.
The concentration of THCP in the cannabis strain tested in the study, an Italian strain called FM2, was particularly low: only 29 micrograms per gram, or 0,0003% of the total. The amount of THC in this strain was also relatively low - only 3,9%.
The researchers noted in the research results that cannabis strains could be improved in the future to contain more THCP, which would also allow it to produce concentrated extracts that could provide an increased medical effect for patients.
The most powerful cannabinoid in the world
During the study, the binding capacity of THCP to cannabinoid receptors (receptors) was tested, and it was found to bind to the CB1 receptor 33 times stronger than THC and to the CB2 receptor 6 times stronger than THC, which makes it the most powerful natural cannabinoid (phytocannabinoid).
In fact, the potency of THCP's attachment to cannabinoid receptors is similar to that of the most potent synthetic cannabinoids, but its structure is almost identical to that of natural THC.
Biological results obtained in the binding test in vitro have indicated an affinity for the CB receptor1 more than thirty times higher than that reported for Δ 9 THC until today. In particular, the Δ 9 -THCP was found to be as active as Δ 9-THC but at lower doses. In fact, the minimum dose of THC used in this type of test is 10 mg / kg, while the Δ 9 -THCP was found to be active at 5 mg / kg in three of the four tetrad tests.
A few decades ago, researchers hypothesized that stronger cannabinoids in cannabis could provide a stronger medical effect, and to test this hypothesis, researchers created from the late 1990s to the present day a wide range of new and more powerful synthetic cannabinoids.
Studies of synthetic cannabinoids generally show very promising results in experiments on mice or isolated tissues, but fail in human trials because of the serious side effects they cause.
But this THCP has a structure almost identical to THC, making it its closest derivative to date. It is hoped that this will provide the "best of both worlds", the increased medical effect of strong cannabinoids, but without the serious side effects associated with synthetic cannabinoids of different structure.
The researchers conducted a preliminary experiment with THCP in mice, and the effect they observed corresponded to the physiological effects typical of THC in mice, including reduced sensitivity to pain, decreased body heat, reduced motor activity and catalepsy (muscle hardening) - but the minimum dose of THC to produce these effects in mice is 10 mg / kg, and here the researchers produced them with only 5 mg / kg of THCP.
In addition to THCP, the researchers also discovered the corresponding derivative of CBD called cannabidipurol or CBDP, but they have not yet tested in depth either the cannabinoid receptors or the mice. Thus, the effects of CBDP are unknown, but it is quite possible that it is also a stronger derivative of CBD.
Studies in progress are devoted to the study of the pharmacological activity of CBDP and the expansion of that of HCP. CBD is known to bind with low affinity for the two CBs 1 and CB 2 receptors. Therefore, assessing the cannabimetic activity of CBDP does not seem to be a high priority, although science may hold great surprises.
The potential of CBDP is not yet as well known as THCP. Like THCP to THC, CBDP shares a chemical structure similar to CBD. In each case, the length of the carbon chain is from five carbon atoms (for THC and CBD) to seven carbon atoms respectively (for THCP and CBDP). Unlike THCP to THC, CBDP does not bind well to cannabinoid receptors (at least in the mice studied in the published article by Nature ).
Because of this low binding potential, studies in the near future are less likely to focus as much on CBDP as they will continue to assess the potential for THCP.
The researchers in the published study predict, however, that CBDP will have effects similar to CBD. It could easily be further developed with applications aimed at relieving pain and anxiety. It may even be able to perform the same functions as CBD pain relievers, but at lower doses due to its concentrated nature. Further study will be necessary to properly assess its potential.
Why this could be great news
The discovery of these two concentrated cannabinoids will likely lend itself to further study on the more potent cannabinoids and will lead to greater availability of cannabinoid products on the market. It has been difficult to isolate some cannabinoids due to their extremely low volume in cannabis plants, but the discovery of these two has the hope of some researchers that other cannabinoid counterparts may be found more easily. Recent research in agricultural genetics has made it possible to select less common cannabis species that produce particularly high amounts of minor phytocannabinoids such as CBDV (cannabidivarin), CBG (cannabigerol) and Δ9-THCV (tetrahydrocannabivarin) other. Other genetic research on strains of cannabis will allow increased production of extracts specifically rich in phytocannabinoids with varied pharmacological profiles that could unlock the potential of a wide range of new remedies for many diseases.