Italian pride - two new cannabinoids discovered - CBDH and Δ 9 -THCH

 Cannabis research has made great progress in recent years in both the clinical and academic fields. While there is still a lot to do in cannabis chemistry research, nearly 150 phytocannabinoids can be counted on the most up-to-date inventory.  

The Italian research team specializing in cannabinoids reports:  

Our most recent works have revealed the existence of new series of phytocannabinoids in addition to those of orcinoids, varinoids and olivetoids, belonging to cannabidiol (CBD) and to cannabinoids of type Δ  ⁹  -tetrahydrocannabinol (Δ  ⁹  -THC). To further complicate the already intricate scenario, we report a new set of phytocannabinoids bridging the gap between the pentyl and heptyl homologs of CBD and Δ  ⁹  -THC, bearing an  n side chain. -exilic on the resorcinyl portion. To the best of our knowledge and according to the literature, no cases of hexyl derivatives of cannabinoids have been reported so far. Conversely, cannabinoids with the same molecular formula and molecular weight have been classified as monomethyl ether derivatives of canonical phytocannabinoids, i.e. cannabigerol monomethyl ether (CBGM), cannabidiol monomethyl ether (CBDM) and Δ  ⁹ -  tetrahydrocannabinol monomethyl ether (Δ  ⁹  -THCM). While CBGM and CBDM have already been isolated and characterized, Δ  ⁹  -THCM has been detected in cannabis smoke and some authors have reported that it is present in the plant but have not been able to isolate it due to chromatographic problems. 

Our results on the presence of the hexyl homologs of CBD and Δ  ⁹  -THC, which we named cannabidihexol (CBDH) and Δ  ⁹  -tetrahydrocannabihexol (Δ  ⁹  -THCH) , respectively, were supported by the stereoselective synthesis of the corresponding pure standards that are found in the plant before decarboxylation. 

IN CONCLUSION

The two most important and studied phytocannabinoids present in  Cannabis sativa  L. are undoubtedly cannabidiol (CBD), a non-psychotropic compound, but with other pharmacological properties, and Δ  ⁹  -tetrahydrocannabinol (Δ  ⁹  -THC), which instead has activity psychotropic and is responsible for the recreational use of hemp. Recently, the homologous series of CBD and THC has been expanded by the isolation in a variety of medicinal cannabis of four new phytocannabinoids that possess on the resorcinyl part a butyl- (in CBDB and Δ  ⁹  -THCB) and a heptyl- (in CBDP and Δ  ⁹-THCP) aliphatic chain. In this work we report a new series of phytocannabinoids that bridges the gap between the pentyl and heptyl homologs of CBD and Δ  ⁹  -THC, bearing an  n -hexyl side chain  on the resorcinyl moiety which we have called cannabidihexol (CBDH) and Δ  ⁹  - tetrahydrocannabiesol ( Δ  ⁹  -THCH), respectively. However, some cannabinoids with the same molecular formula and molecular weight as CBDH and Δ  ⁹  -THCH have already been identified and reported as monomethyl ether derivatives of canonical phytocannabinoids, namely cannabigerol monomethyl ether (CBGM), cannabidiol monomethyl ether (CBDM ) and Δ  ⁹-tetrahydrocannabinol monomethyl ether (Δ9-THCM). The unambiguous identification in the cannabis extract of the  n  -hexyl homologs of CBD and Δ  ⁹  -THC other than the corresponding methylated isomers (CBDM, CBGM and Δ  ⁹  -THCM) was obtained by comparing the retention time, molecular ions and fragmentation spectra with those of authentic standards obtained by stereoselective synthesis, and a semi-quantification of these cannabinoids in the FM2 medical cannabis variety was provided. Conversely, no trace of Δ  ⁹-THCM was detected. Furthermore, CBDH was isolated by semipreparative HPLC and its identity was confirmed by comparison with the spectroscopic data of the corresponding synthetic standard. Therefore, the correct recognition of CBDH, CBDM and Δ  ⁹  -THCH closes the cycle and could serve researchers in the future to distinguish between these phytocannabinoid isomers that exhibit very similar analytical behavior. Finally, CBDH was evaluated for in vivo biological tests showing interesting analgesic activity at low doses in mice.

 

From this study it is also possible to understand how cannabis is one of the few plants that contains a surprisingly wide and varied chemical composition, from this it can be predicted that by knowing it in depth it is possible to use a certain variety for each specific pathology.

 

The research group is composed of: 

• Pasquale Linciano  ,
• Cinzia Citti  ,
• Fabiana Russo  ,
• Francesco Tolomeo  ,
• Aldo Laganà  ,
• Anna Laura Capriotti  ,
• Livio Luongo  ,
• Monica Iannotta  ,
• Carmela Belardo  ,
• Sabatino Maione  ,
• Flavio Forni  ,
• Maria Angela Vandelli  ,
• Giuseppe Gigli  &
• Giuseppe Cannazza 

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