Researchers develop new method for synthesising a cannabis plant active ingredient

„With our strategy, it is now possible to produce cis-tetrahydrocannabinoids and investigate their biological activity“, explains researcher Caroline Dorsch, who published her new findings together with Prof. Dr Christoph Schneider from the Institute of Organic Chemistry in the journal „Applied Chemistry“. Dr Christoph Schneider from the Institute of Organic Chemistry in the journal „Angewandte Chemie“.

Until now, there has been no way to synthesise this class of structures uniformly, she emphasises. With their synthesis method, which is as simple as it is cost-effective and closely modelled on nature, the Leipzig researchers have made the substance class of cis-tetrahydrocannabinoids accessible for broad application for the first time. It is clearly superior to previous methods, which required many steps and large quantities of chemicals and solvents. With the new method, the substance can be synthesised in high overall yields and with excellent optical purity.

Tetrahydrocannabinol is one of the phytocannabinoids produced in the cannabis plant. These compounds accumulate primarily in the flower stalks of female plants. It has been known since the 1960s that this also causes the characteristic psychotropic effect in the body. Research into this natural substance led to the elucidation of the underlying mechanism of its effect - the endocannabinoid system. This is the name given to the signalling transduction pathway in the body that tetrahydrocannabinol influences and which causes the characteristic effect, for example when smoking marijuana.

„Influencing this signalling pathway is of pharmaceutical relevance. Cannabinoids can have a variety of effects in the body, for example as painkillers, antipsychotics or antiepileptics. However, there are currently only a few cannabinoids on the pharmaceutical market. The prescription of natural cannabis products is sometimes considered an exception," says Dorsch. The possession, cultivation and distribution of narcotic cannabis products is prohibited in Germany under the Narcotics Act. Samples containing trans-configured cannabinoids are classified as narcotic. Recent studies have shown that cis-THC mainly accumulates in parts of the cannabis plant that lack the related trans-compounds. This has so far led to the classification of such samples as textile or non-narcotic hemp. However, cis-THC exhibits mild psychotropic activity.

THC is a chiral compound. Chirality describes a spatial arrangement of atoms in a molecule in which mirroring does not lead to self-imaging. The image and mirror image of such compounds are known as enantiomers and often have different effects in the human organism. Nature can easily control the targeted synthesis of these compounds. Under laboratory conditions, however, this is a major challenge, which was successfully overcome in the present work. The newly developed process also requires very small amounts of the catalyst, which is also very attractive from an ecological point of view in terms of saving energy and resources and minimising by-products.

Cis-THC has so far been less of a focus of research than the more potent trans-THC due to its milder psychotropic activity. Nevertheless, other natural compounds that are not derived from cannabis also share a basic structure with cis-THC. These are valuable compounds whose promising pharmacological activity profile has not yet been fully explored. The new strategy now presented has laid an important foundation for a more detailed investigation of this family of substances. Using this method, a number of other natural and non-natural representatives of this structural class could be produced in addition to cis-THC.

Press release of the "idw - Informationsdienst Wissenschaft" from 17 May 2023