Chemistry:Hexahydrocannabinol

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Hexahydrocannabinol (HHC) is a phytocannabinoid that has been reported as a trace component of Cannabis sativa.[1][2] It can also be synthesized by hydrogenation of tetrahydrocannabinol (THC). The synthesis and bioactivity of HHC was first reported in 1940 by Roger Adams.[3]

HHC is a psychoactive substance with effects reportedly similar to those 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.[4][5] HHC has no known medical uses, however a racemic mixture of epimers has shown in vitro activity against pancreatic ductal adenocarcinoma cell lines.[6]

Pharmacology

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.[7][8]

Chemistry

Several research groups have successfully synthesized (+)-HHC and (-)-HHC using citronellal and olivetol,[9] as well as other related compounds.[10] While similar compounds have previously been identified in cannabis,[11] 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.[12][13]

Several structurally related HHC analogs have been found to be naturally occurring in Cannabis including cannabiripsol,[14] 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexa-hydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10aR-hydroxyhexahydrocannabinol and 1′S-hydroxycannabinol,[11] 10α-hydroxy-Δ(9,11)-hexahydrocannabinol and 9β,10β-epoxyhexahydrocannabinol.[15]

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.[16][17]

Delta-9-THC was discovered to partly metabolize into 11-hydroxy-THC and alpha,10 alpha-epoxy-hexahydrocannabinol along with 1,2-epoxy-hexahydrocannabinol.[18] 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.[19]


Legality

In Ireland, HHC was classified as an illegal drug by the Government on 29 July 2025. This was on the advice of the Health Service Executive of Ireland, which stated that "since it (HHC) was first detected in Ireland in 2022, it has been linked with episodes of psychosis and hospitalisation".[20]

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).[21]

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.[22][23]

HHC has been banned in Sweden since 11 July 2023, and in Italy since 28 July 2023.[24]

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.[25]

HHC has been banned in Lithuania since 23 November 2022, and in Slovenia since 15 November 2023.[26]

HHC has been banned in the Czech Republic since 6 March 2024.[27]

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) (de) in a meeting on 4 December 2023.[28] 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.[29]

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."[30]

HHC has been banned in Poland as of 14 April 2023.

See also

References

  1. ↑ "Phytocannabinoids: a unified critical inventory". Natural Product Reports 33 (12): 1357–1392. November 2016. doi:10.1039/c6np00074f. PMID 27722705. 
  2. ↑ "GC-MS Metabolite Profile and Identification of Unusual Homologous Cannabinoids in High Potency Cannabis sativa". Planta Medica 86 (5): 338–347. March 2020. doi:10.1055/a-1110-1045. PMID 32053835. 
  3. ↑ "Structure of Cannabidiol. VI. Isomerization of Cannabidiol to Tetrahydrocannabinol, a Physiologically Active Product. Conversion of Cannabidiol to Cannabinol". Journal of the American Chemical Society 62 (9): 2402–2405. September 1940. doi:10.1021/ja01866a040. 
  4. ↑ European Monitoring Centre for Drugs and Drug Addiction. (2023). Technical Report: Hexahydrocannabinol (HHC) and related substances. European Monitoring Centre for Drugs and Drug Addiction. doi:10.2810/852912. ISBN 978-92-9497-855-4. https://www.emcdda.europa.eu/publications/technical-reports/hhc-and-related-substances_en. 
  5. ↑ "Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review". Drug Testing and Analysis 16 (2): 127–161. 2024. doi:10.1002/dta.3519. PMID 37269160. 
  6. ↑ "Synthesis, Characterization, and in vitro Experiments of Saturated Cannabinoids on Pancreatic Ductal Adenocarcinoma Cell Lines (HPAF-II, MIA-PaCa2, ASPC-1, and PANC-1)". Natural Product Communications 20 (6): 1–11. June 2025. doi:10.1177/1934578X251348390. 
  7. ↑ "Studies Pertaining to the Emerging Cannabinoid Hexahydrocannabinol (HHC)". ACS Chemical Biology 18 (9): 2023–2029. September 2023. doi:10.1021/acschembio.3c00254. PMID 37578929. 
  8. ↑ "Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review". Drug Testing and Analysis 16 (2): 127–161. February 2024. doi:10.1002/dta.3519. PMID 37269160. 
  9. ↑ "Efficient one-pot synthetic approaches for cannabinoid analogues and their application to biologically interesting (-)-hexahydrocannabinol and (+)-hexahydrocannabinol". Tetrahedron Letters 49: 3283. 2008. doi:10.1016/j.tetlet.2008.03.075. 
  10. ↑ "Enantioselective Total Synthesis of Potent 9β-11-Hydroxyhexahydrocannabinol". The Journal of Organic Chemistry 85 (2): 1291–1297. January 2020. doi:10.1021/acs.joc.9b02962. PMID 31833372. 
  11. ↑ 11.0 11.1 "Minor oxygenated cannabinoids from high potency Cannabis sativa L". Phytochemistry 117: 194–199. September 2015. doi:10.1016/j.phytochem.2015.04.007. PMID 26093324. Bibcode: 2015PChem.117..194A. 
  12. ↑ "In vitro metabolism of the equatorial C11-methyl isomer of hexahydrocannabinol in several mammalian species". Drug Metabolism and Disposition 19 (3): 714–716. May 1991. PMID 1680642. http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1680642. 
  13. ↑ "Comparative in vitro metabolism of the cannabinoids". Pharmacology, Biochemistry, and Behavior 40 (3): 533–540. November 1991. doi:10.1016/0091-3057(91)90359-a. PMID 1806943. 
  14. ↑ "Cannabiripsol: a novel Cannabis constituent". Experientia 35 (10): 1278–1279. October 1979. doi:10.1007/BF01963954. PMID 499397. 
  15. ↑ "Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa". Journal of Natural Products 78 (6): 1271–1276. June 2015. doi:10.1021/acs.jnatprod.5b00065. PMID 26000707. 
  16. ↑ "Constituents of Cannabis sativa L. IV. Stability of cannabinoids in stored plant material". Journal of Pharmaceutical Sciences 62 (10): 1601–1605. October 1973. doi:10.1002/jps.2600621005. PMID 4752104. 
  17. ↑ "Stability of tetrahydrocannabinols II". Journal of Pharmaceutical Sciences 67 (1): 27–32. January 1978. doi:10.1002/jps.2600670108. PMID 22740. 
  18. ↑ "Cytochrome P-450 isozymes involved in the oxidative metabolism of delta 9-tetrahydrocannabinol by liver microsomes of adult female rats". Drug Metabolism and Disposition 20 (1): 79–83. January 1992. PMID 1347001. http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1347001. 
  19. ↑ "Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature". Toxics 8 (2): 41. June 2020. doi:10.3390/toxics8020041. PMID 32503116. 
  20. ↑ https://www.rte.ie/news/health/2025/0729/1525933-hhc-drug-ban/ [bare URL]
  21. ↑ "Office for Tobacco Coordination - News and Product Warnings - AGES - Hexahydrocannabinol (HHC), new regulation in the NPSV". https://www.ages.at/en/ages/office-for-tobacco-coordination/news-and-product-warnings#accordion-24442. 
  22. ↑ "Cannabis : le HHC sera interdit en France à partir de mardi" (in fr). Le Monde.fr. 2023-06-12. https://www.lemonde.fr/sante/article/2023/06/12/cannabis-le-hhc-sera-interdit-en-france-a-partir-de-mardi_6177293_1651302.html. 
  23. ↑ "Actualité - L'ANSM classe l'hexahydrocannabinol (HHC) et deux de ses dérivés sur la liste des stupéfiants" (in fr). https://ansm.sante.fr/actualites/lansm-classe-lhexahydrocannabinol-hhc-et-deux-de-ses-derives-sur-la-liste-des-stupefiants. 
  24. ↑ "Gazzetta Ufficiale". https://www.gazzettaufficiale.it/atto/serie_generale/caricaDettaglioAtto/originario?atto.dataPubblicazioneGazzetta=2023-07-25&atto.codiceRedazionale=23A04164&elenco30giorni=true&fbclid=IwAR0d8pv68emAlSwx5PPesHph7DtpXGIfcfaIaSbHuNDnEcBWRZf4ws750Ag. 
  25. ↑ "Hexahydrocannabinol (HHC) to be Regulated in Luxembourg". https://chronicle.lu/category/medical/46193-hexahydrocannabinol-hhc-to-be-regulated-in-luxembourg. 
  26. ↑ "eUprava - Predlog predpisa". https://e-uprava.gov.si/si/drzava-in-druzba/e-demokracija/predlogi-predpisov/predlog-predpisa.html?id=15805. 
  27. ↑ "Začíná platit zákaz držení a prodeje produktů s HHC, HHC-O a THCP". 6 March 2024. https://www.seznamzpravy.cz/clanek/domaci-zivot-v-cesku-zacina-platit-zakaz-drzeni-a-prodeje-produktu-s-hhc-hhc-o-a-thcp-247181. 
  28. ↑ "Sachverständigenausschuss für Betäubungsmittel nach § 1 Abs. 2 BtMG und Neue-psychoaktive-Stoffe nach § 7 NpSG" (in de). https://www.bfarm.de/DE/Bundesopiumstelle/Betaeubungsmittel/Sachverstaendigenausschuss/Sitzungen/Ergebnisse_59.html?nn=595366. 
  29. ↑ "Status of chemicals in the Russian Federation" (in Russian). 1 May 2024. https://besedina.moscow/messaging/728. 
  30. ↑ "Watch: Malta bans HHC products 'to protect children, public health'" (in en-gb). 2024-09-27. https://timesofmalta.com/article/watch-malta-bans-hhc-products-to-protect-children-public-health.1098676. 



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