Unlike synthetic cannabinoids, the semi-synthetic cannabinoids are mostly produced from cannabidiol extracted from low-THC cannabis (hemp) – the production and availability of which has proliferated in recent years in the United States and Europe.

In 2022, semi-synthetic cannabinoids, which are not controlled under the international drug conventions, started to appear on the European drug market. The first was hexahydrocannabinol (HHC) in May. Five other semi-synthetic cannabinoids, HHC acetate (HHC-O), hexahydrocannabiphorol (HHC-P), tetrahydrocannabidiol (H4-CBD​), tetrahydrocannabiphorol (THC-P) and hexahydrocannabihexol (HHCH) have also been identified.

HHC appears to have first been sold in the United States in or around September 2021, although the precise date is unknown. HHC is one of a number of semi-synthetic cannabinoids that have recently been sold openly in the US as legal replacements for cannabis and delta-9-THC, beginning with delta-8-tetrahydrocannabinol (delta-8-THC) in 2019. This new market is associated with:

• the legalisation of hemp cultivation in the US in 2018;
• subsequent abundant or surplus supply of hemp and hemp-derived cannabidiol (CBD), which can be used as a precursor for semi-synthetic cannabinoids;
• the interpretation by producers that cannabinoids derived from hemp are not controlled under the US Federal Controlled Substances Act, so long as the final product does not contain more than 0.3 % delta-9-THC by dry weight.

Since then, these products have also begun to proliferate in Europe. At least initially, bulk quantities of HHC and some other semi-synthetic cannabinoids, in the form of oils or distillates, as well as consumer products were imported into Europe.