Δ9-Tetrahydrocannabiphorol: Identification and quantification in recreational products

Abstract

Δ9-Tetrahydrocannabinol (Δ9-THC) is known to be the component of the cannabis plant responsible for the psychoactive effects generated by the activation of the endocannabinoid receptor 1 (CBR1). Following extensive structure–activity relationship (SAR) studies on Δ9-THC, new molecules with increased CBR1 affinity were designed and synthesized over the last decades. The knowledge arising from the pharmacological and synthetic investigations has been extensively used in the recent past by the industry of substances for recreational use also thanks to the 2018 Farm Bill Act in the USA and the incentive for low-THC cannabis (hemp) cultivation in Europe, which have boosted the availability of hemp derived precursors.As a result, new semi-synthetic natural and pseudo natural cannabinoids related to the most famous Δ9-THC and often not subjected to legal restrictions are now available in the online market in a broad array of retail products with no preventive study on their pharmacodynamics and pharmacokinetics.Some of these products (gummies, cannabis flower and a vape cartridge), all declared to contain the most potent among all the known cannabinoids, Δ9-Tetrahydrocannabiphorol (Δ9-THCP), were bought from an online shop and tested through LC-HRMS to determine the effective amount of Δ9-THCP and of other cannabinoids.All the three samples were found to contain Δ9-THCP in amounts significantly different from those declared by the producer. Moreover, the application of an untargeted metabolomics approach (cannabinomics) enabled the identification of other cannabinoids including the emerging semi-synthetic hexahydrocannabinol (HHC) and tetrahydrocannabidiol (H4-CBD) together with byproducts of synthetic origin.