Short Lecture "Pharmacokinetics, behavioural and cannabinoids receptor binding profile of hemp derived (R/S)-Hexahydrocannabinol"

The use of cannabis plant dates to ancient China around 2500 BC. Cannabinoids, which are found naturally in plants, have been widely used for recreational and medicinal purposes. Cannabis sativa L. produces more than 150 cannabinoids, which most of them occurred in only trace amounts. Δ9-THC is the main compound responsible for the intoxicant activity of cannabis plant and thus the plant containing higher amount of Δ9- THC is regulated according to the UN Convention. The community of recreational cannabis users rediscovered the very rare natural cannabinoids (R/S)-Hexahydrocannabinol (HHC) as the demand for the legal alternatives of Δ9-THC. HHC edibles and vape liquids are in the Czech Republic available freely in shops and even vendor machines, which cause a series of intoxications. Although the HHC was firstly synthesised from Δ9-THC in 1947, the pharmacological and behavioural study has not been performed so far. We prepared the pure (R) and (S) enantiomers of HHC. Pharmacokinetics and behavioural tests in Wistar rats were performed following gastric administration of R/S HHC. Behavioural experiments (open field test, PPI, ASR and conditioned place preference) have a standardised design in order to obtain comparable data to Δ9-THC. Pharmacokinetics profile was measured in rats’ serum using LC-MS. The binding affinities of the both R/S HHC enantiomers to CB1 receptor and beta-arrestin2-CB1R interaction were compared to Δ9-THC and WIN 55,212-2. Pharmacokinetics and behavioural profile in animal model with Wistar rats figured out similarities with Δ9-THC but with significant differences of each enantiomer.

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Artikel online veröffentlicht:
16. November 2023