• Source: Hexahydrocannabinol

Hexahydrocannabinol (HHC) is a hydrogenated derivative of tetrahydrocannabinol (THC). It is a naturally occurring phytocannabinoid that has rarely been identified as a trace component in Cannabis sativa, but can also be produced synthetically by firstly acid cyclization of cannabidiol and then hydrogenation of tetrahydrocannabinol. The synthesis and bioactivity of HHC was first reported in 1940 by Roger Adams.
HHC is a psychoactive substance with effects reportedly similar to that of THC. HHC vaporizers have been openly sold at head shops and convenience stores since at least the early 2020s in North America and Europe.




Pharmacology


HHC has 2 diastereomers that only differ by the orientation of the 9-methyl group, unlike D9-THC and D8-THC which have the double bond position next to the 9-methyl group that prevents this. The 9-methyl group orientation is believed to be important for cannabinoid binding affinity.
Research has found 9R-HHC to have a binding affinity of 15nM ± 0.8nM at CB1 and 13nM ± 0.4nM at CB2, while 9S-HHC has a binding affinity of 176nM ± 3.3nM at CB1 and 105nM ± 26nM at CB2.
The same study found Delta-9-THC to have a binding affinity of 15nM ± 4.4nM at CB1 and 9.1nM ± 3.6nM at CB2. 9R-HHC has a lower selectivity for CB2 (1.2x) compared to D9-THC (1.6x).
9R-HHC has an EC50 of 3.4nM ± 1.5nM at CB1 and 6.2nM ± 2.1nM at CB2 while 9S-HHC has an EC50 of 57nM ± 19nM at CB1 and 55nM ± 10nM at CB2. The same study found D9-THC to have an EC50 of 3.9nM ± 0.5nM at CB1 and 2.5nM ± 0.7nM at CB2.
The EC50 shows 9R-HHC has a lower selectivity for CB2 (0.55x) compared to THC (1.5x). HHC has been typically described as weaker than Delta-9-THC in psychoactive effects. HHC produces 11-Hydroxyhexahydrocannabinol and 8-Hydroxyhexahydrocannabinol among others as a metabolite which may contribute to its overall effect.




Chemistry


Several research groups have successfully synthesized (+)-HHC and (-)-HHC using citronellal and olivetol, as well as other related compounds. While similar compounds have previously been identified in cannabis, hexahydrocannabinol itself has rarely been isolated from the plant. The de Las Heras group in 2020 took lipid extract from Cannabis sativa seeds and discovered 43 cannabinoids in the crude extract; one of them being hexahydrocannabinol. It has two diastereomers at the methyl (9) position. HHC is typically made from hydrogenation of THC. There are no double bonds in the cyclohexyl ring like D8/D9 have—they have been removed from the structure and hydrogens have been added to the compound.
Several structurally related HHC analogs have been found to be naturally occurring in Cannabis including cannabiripsol, 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexa-hydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10aR-hydroxyhexahydrocannabinol and 1′S-hydroxycannabinol, 10α-hydroxy-Δ(9,11)-hexahydrocannabinol and 9β,10β-epoxyhexahydrocannabinol.
HHC itself has been found as a degradation byproduct of THC in a similar way that Cannabinol and Delta-8-THC can be formed by the Cannabis plant from Delta-9-THC degradation. The degradation of D9-THC that forms HHC is the reduction of the double carbon bonds that would typically make up the delta isomer position on THCs structure.
Delta-9-THC was discovered to partly metabolize into 11-Hydroxy-THC and alpha,10 alpha-epoxy-hexahydrocannabinol along with 1,2-epoxy-hexahydrocannabinol. Cannabidiol was discovered to partly metabolize into 9α-hydroxy-HHC and 8-hydroxy-iso-HHC inside the body. In the presence of alcohol, the methoxy or ethoxy analogs such as 9-methoxy-HHC, 10-methoxy-HHC, 9-ethoxy-HHC and 10-ethoxy-HHC can be formed.
Hexahydrocannabinol should not be confused with the related compounds 9-Nor-9β-hydroxyhexahydrocannabinol (9-Nor-9Beta-HHC) or 9-Hydroxyhexahydrocannabinol (9-OH-HHC) or 11-Hydroxyhexahydrocannabinol (11-OH-HHC and 7-OH-HHC), all of which have also sometimes been referred to as "HHC".




Legality


[MAP OF HHC LEGALITY IN EUROPE HAS BEEN REMOVED DUE TO CONTAINING OUTDATED INFORMATION]
In the United Kingdom, HHC would likely be considered illegal under the Psychoactive Substances Act 2016. Although HHC is covered by the Psychoactive Substances Act 2016 in the UK, it is not explicitly listed in the legislation. As a result, penalties associated with HHC may be less severe compared to other, explicitly mentioned substances like for example THC.
Several European countries (Denmark, Belgium) banned the sale of HHC in 2023.
In Austria, HHC has been banned since 23 March 2023 due to the amendment of the New Psychoactive Substances Ordinance (known in German as Neue-Psychoaktive-Substanzen-Verordnung or NPSV).
In France, the ANSM announced the ban on production, sale and use of HHC and two of its derivatives, HHCO and HHCP, from 13 June 2023.
HHC has been banned in Sweden since 11 July 2023, and in Italy since 28 July 2023.
In Luxembourg, Ministry of Health announced on 1 August 2023 that HHC would be regulated in that country by extending its list of psychotropic substances from 2009 to all "synthetic cannabinoid receptor agonists" and "synthetic cannabinomimetics [sic]", with semi-synthetic cannabinoids such as HHC falling within the scope of that regulation.
HHC has been banned in Lithuania since 23 November 2022, and in Slovenia since 15 November 2023.
HHC has been banned in the Czech Republic since 6 March 2024.
In Germany, manufacture and sale of products containing HHC and other synthetically produced cannabinoids, such as THCP and HHCP, became outlawed on 27 June 2024 (possession and consumption of those products remain legal). Previously, the German expert committee for narcotics had suggested that HHC be added to the annex of Novel Psychoactive Substances Act (NpSG) in a meeting on 4 December 2023. This recommendation was enacted by the Bundesrat on 14 June 2024, and was published in the Bundesgesetzblatt on 26 June.
In Russia, Deputy of the Moscow City Duma Darya Besedina sent a request on 1 March 2024 to the Russian Ministry of Internal Affairs to clarify the legal status of HHC, HHCP and THCP in Russia. According to the answer from the Ministry that Besedina published, HHC and HHCP are not prohibited in Russia, but THCP is banned.
In Malta, Parliamentary Secretary of Reforms and Equality Rebecca Buttigieg announced on 27 September 2024 that "all HHC products will be banned from Maltese markets."
HHC has been banned in Poland as of 14 April 2023.




See also


8-Hydroxyhexahydrocannabinol
11-Hydroxyhexahydrocannabinol
7,8-Dihydrocannabinol
Cannabinol
9-Nor-9β-hydroxyhexahydrocannabinol
9-Hydroxyhexahydrocannabinol
H4-CBD
Hexahydrocannabihexol
HU-243
Canbisol
Delta-8-THC
Delta-10-THC
Delta-11-THC
Tetrahydrocannabiphorol
THC-O-acetate
Delta-6-Cannabidiol




References

Kata Kunci Pencarian:

• Hexahydrocannabinol
• Hexahydrocannabiphorol
• HHC-acetate
• HHCP-O-acetate
• Hexahydrocannabihexol
• H4-CBD
• 11-Hydroxyhexahydrocannabinol
• CP 42,096
• Cannabiripsol
• Cannabis (drug)