A group of Italian researchers, led by Professor Giuseppe Cannazza of the University of Modena and Reggio Emilia (UniMore), has discovered a new cannabinoid more than 30 times more potent than THC. Upon discovery, they named it tetrohydrocannabiforol (Δ9-THCP) and isolated it along with a corresponding cannabidiol (CBD) homolog with a seven-term side alkyl chain, cannabidiforol (CBDP).
Their study, published on December 30th, 2019, in Scientific Reports, shows that THCP binds to both human CB1 and CB2 receptors of the endocannabinoid system—and was 33 times more active than THC, 63 times more active than THCV, and 13 times more active than the newly discovered THCB against CB1 receptor. The suffix “-phorol” comes from “sphaerophorol”, common name for 5-heptyl-benzen-1,3-diol.
The research of the new cannabinoids started by studying industrial hemp. As marijuana is illegal in Italy, researchers needed to ask permission to study the plant from Italy’s Ministry of Health. Right now, the Military Pharmaceutical Chemical Plant in Florence is the only state agency authorized to cultivate medical cannabis strains provided by the Council for Agricultural Research and Agricultural Economy Analysis (CREA).
“We have discovered these new cannabis compounds because no one was looking for them”, Dr Cannazza explained.
Researchers found the new phytocannabinoid, cannabidiforol (CBDP), with a structure similar to CBD. “Our colleague, Dr. Cinzia Citti, thought there could be a correspondent of CBDP— THCP. Upon the authorization from Italy’s Ministry of Health, we had the opportunity to study the FM2 cannabis strain cultivated by the Military Pharmaceutical Chemical Plant in Florence,” said Dr. Cannazza.
During research on the FM2 strain, a phytocannabinoid with the same structure as THC was discovered, but with a seven-term alkyl chain. Cannazza explained that, “THCP has a longer alkyl chain and it is more lipophilic and fits the CB1 receptors 30 times more than THC. We only did a drug study but now the adventure begins, because this is only the first step towards this new class of cannabinoids.”
According to the study, to date, naturally occurring cannabinoids with a linear alkyl side chain longer than five terms have never been detected or identified in cannabis plants. THCP molecular structure was identified with a seven-term alkyl side chain.
Through a tetrad test on mice, THCP caused hypomotility, analgesia, catalepsy, and decreased rectal temperature, indicating a cannabimimetic activity similar to THC. According to Dr. Cannazza, the presence of this new phytocannabinoid could explain why the pharmacological properties of some cannabis is difficult to determine due to the presence of the only THC.
“This means that we have to study the concentration of THCP and CBDP cannabinoids in the different cannabis strains because sometimes it is not clear why some strains with a low THC level have extremely high psychotropic properties: it could [probably] be due to THCP.”
The goal of the research was to give a molecular imprint to the FM2 strain. The researchers worked with a new technique, called metabolomics, which is the systematic study of the chemical footprints left by specific cellular processes and which allows the identification of a molecular footprint of the biological sample and enables the discovery and identification of new compounds with a high degree of confidence, even when present in traces in complex matrices.
Researchers have found that in vitro and in vivo preliminary studies on THCP showed a cannabimimetic activity 30 times higher than THC. In fact, the biological results indicated an affinity between THCP and the CB1 receptor 30 times higher than the affinity that this receptor has for THC. “According to tests on mice, THCP is much more powerful than THC, but it will be necessary to understand what happens in humans,” explained Dr. Cannazza.
Why We Should Care
The importance of this discovery lies in the fact that, so far, no one has ever looked for this powerful phytocannabinoid. According to the researchers, this discovery could shed light on several pharmacological effects not attributable exclusively to THC.
“The next step will be to research the concentration of these cannabinoids in other cannabis varieties to find out why some varieties with a low THC level have extremely high psychotropic properties and one answer would be THCP. As for CBDP, on the other hand, we know absolutely nothing at the moment ”, explained Dr. Cannazza.
Research on THCP is still in its infancy, while CBDP hasn’t been studied yet, even though it was discovered before THCP.
The discovery of THCP is part of a 3-year project on hemp with a budget of 300 thousand euros. The funds were allocated by the European Union.
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