New Year, New Cannabinoids

An interview with Giuseppe Cannazza of the Department of Life Sciences at the University of Modena and Reggio Emilia and the Institute of Nanotechnology of the National Council of Research (CNR NANOTEC) regarding the discovery of two new cannabinoids—Δ⁹-tetrahydrocannabiphorol (THCP) and cannabidiphorol (CBDP).

On December 30, 2019, researchers from the Department of Life Sciences at the University of Modena and Reggio Emilia and the Institute of Nanotechnology of the National Council of Research (CNR NANOTEC) in Italy published an exciting manuscript in Scientific Reports on nature.com identifying two new cannabinoids: Δ⁹-tetrahydrocannabiphorol (THCP) and cannabidiphorol (CBDP) (1). In this installment of “Cannabis Crossroads,” we gain insights from the lead author and researcher, Giuseppe Cannazza, regarding these discoveries.

The identification of two new cannabinoids is extremely exciting. Please share details on how these new cannabinoids were discovered. Are these cannabinoids present at very low concentrations in most commercial cannabis strains?

Giuseppe Cannazza: The first intuition about the possible presence of a cannabinoid with a seven-term alkyl chain, in particular CBDP, came from Dr. C. Citti, who was analyzing the chemical composition of a hemp extract by mass spectrometry (MS). From here I hypothesized that also the THC counterpart could be present in a medicinal cannabis variety since hemp contains very low amounts of THC-like compounds. The Italian Ministry of Health gave us the authorization to study the FM2 cannabis variety, which is produced by the Military Chemical Pharmaceutical Institute of Florence, and we were able to demonstrate our hypothesis. The concentration present in this variety is extremely low and probably it does not reach the effective dose to produce a pharmacological effect. It should not be ruled out though that the concentration of THCP might be higher in other cannabis varieties, since this compound has never been searched for in the plant before. Thanks to Dr. P. Linciano’s work, we now have the pure standard.

One of the new cannabinoids is reported to have 30 times affinity for cannabinoid receptors. What exactly does this mean? Is this affinity for a specific receptor type?

Cannazza: THCP was tested in vitro on CB1 and CB2 receptors proving to have a 33-fold affinity for CB1 compared to the data on THC reported in the literature. This does not mean that it is active in vivo. Therefore, Dr. L. Luongo tested THCP on mice to evaluate its cannabimimetic activity. The results suggest that THCP acts similarly to THC but at lower doses (about half dose).

Are the high-resolution MS techniques you used to find and identify these cannabinoids amenable to finding additional cannabinoids? Are you currently working to identify new ones now?

Cannazza: We are going on with our research to study the chemical composition of different cannabis varieties. We started with cannabidibutol (CBDB) and Δ⁹-tetrahydrocannabutol (THCB), the corresponding derivatives with a four-term alkyl chain, published in the Journal of Natural Products (2), then we studied CBDP and THCP. We are now looking for CBGB, CBGP, CBCB, CBCP, and so on.

You stated that a phytocannabinoid with a linear alkyl side chain containing more than five carbon atoms has never been reported as naturally occurring. Is this cannabinoid more likely to cross the blood-brain barrier? Any other physiological significance here?

Cannazza: No pharmacokinetic test was performed on CBDP and THCP. We can only speculate that they are more lipophilic molecules than the respective CBD and THC and therefore they could cross the blood-brain barrier more easily by passive diffusion. However, the road is still long for a clear understanding of their biological activity.

Thank you for sharing information on these groundbreaking discoveries. Do you have any final thoughts that you would like to share here, or any comments on your laboratory’s future directions?

Cannazza: There is still a long way to accomplish a comprehensive characterization of cannabinoids in a cannabis variety, but our work will pave the way for pharmacologists, toxicologists, and clinicians for the correlation of the observed biological effects with the chemical composition of the different cannabis varieties used.

References

1. G. Cannazza, et. al, Sci. Rep.9, 20335 (2019) doi:10.1038/s41598-019-56785-1.
2. P. Linciano, C. Citti, L. Luongo, C. Belardo, S. Maione, M.A. Vandelli, F. Forni, G. Gigli, A. Laganà, C.M. Montone, and G. Cannazza, J. Nat. Prod. (2019), https://doi.org/10.1021/acs.jnatprod.9b00876.

About the Interviewee

Giuseppe Cannazza is a researcher at the University of Modena and Reggio Emilia, where he leads a research group in the Department of Life Sciences that develops analytical methods for the study of cannabis extracts. He is also an Associate Researcher at CNR NANOTEC of LECCE, where he leads another research group that develops advanced analytical methods for the comprehensive chemical characterization of plant material. He has been responsible for regional and national projects. He is the author of more than 73 publications in peer-reviewed international journals. He has been an invited speaker to several seminars in Italy and abroad on the different uses of cannabis. He has been selected as author of the Chemistry reports on cannabis plant and resin, extracts of cannabis, THC and THC isomers for the 40th Expert Committee on Drug Dependence (ECDD) of World Health Organization (WHO). He was an adviser for the 40th ECDD held in Geneva, Switzerland in 2018.

About the Columnist

Joshua Crossney is the columnist and editor of “Cannabis Crossroads” and a contributing editor to Cannabis Science and Technology magazine. Crossney is also the president and CEO of CSC Events. Direct correspondence to: josh@jcanna.com

How to Cite This Article

J. Crossney, Cannabis Science and Technology 3(1), 26-27 (2020).