Semi-synthetic cannabinoid
Narcotic: generic clause(9S)-HHC(9S)-Hexahydrocannabinol
(6aR,9S,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol
Aliases.9S-HHC · 9(S)-Hexahydrocannabinol · S-épimère du HHC
The 9S epimer of HHC, the twin form far less active than (9R).
Updated on
Level of detail
Harm-reduction warning
No characterised human dose: animal / in vitro data only. Effect profile, safety margin and acute toxicity are not documented in human clinical practice. Extremely potent compound: severe effects, seizures and deaths reported in the literature.
Identifiers
- Formula
- C₂₁H₃₂O₂
- Molar mass
- 316.50 g·mol⁻¹
- CAS
- 36403-91-5
- PubChem CID
- 14378541
- First described
- Décrit dès les années 1940 par les travaux de Roger Adams sur l'hydrogénation des cannabinoïdes, puis caractérisé comme épimère distinct dans les études pharmacologiques modernes du HHC.
- Origin
- semisynthetic
- InChIKey
- XKRHRBJLCLXSGE-USXIJHARSA-N
In plain terms
(9S)-HHC is one of the two "faces" of HHC. It is the twin form, far less active, always found mixed with its counterpart in HHC-based products.
Receptors and activity
- CB1Partial agonist
- CB2Partial agonist
- Agonist
- Partial agonist
- Antagonist
- Modulator
- Inverse agonist
Hover over a row for the precise value (Ki, EC50…)
Subjective signature
Hover over an axis to read its definition.
- Calm30
- Clarity15
- Sleep28
- Appetite25
- High20
Editorial estimate, not clinical.
Pharmacology
(9S)-HHC is the 9S epimer of hexahydrocannabinol, systematically co-present with (9R)-HHC in marketed HHC. Both epimers bind to the CB1 and CB2 receptors as Δ9-THC-type partial agonists, but the cannabimimetic activity resides chiefly in the 9R epimer: (9S)-HHC is the less potent of the two, a difference attributed to its less favourable conformation in the receptor's active site (a chair / twist-boat equilibrium placing the C9 methyl unfavourably). In France it falls under the narcotics regime applicable to HHC and its hydrogenated derivatives.
Key sources.
- Synthesis and pharmacological activity of the epimers of hexahydrocannabinol (HHC), Scientific Reports 2023DOI 10.1038/s41598-023-38188-5
- Origin of the Different Binding Affinities of (9R)- and (9S)-Hexahydrocannabinol (HHC) for the CB1 and CB2 Cannabinoid Receptors, ACS Chemical Biology 2025PMID 40704858
- In vitro activation of the CB1 receptor by the semi-synthetic cannabinoids HHC, HHC-O and HHC-P, Drug Testing and Analysis 2025PMID 38894658
- PubChem CID 14378541 : 9S-HHC (identifiers)
- Décision ANSM du 22 mai 2024 portant modification de la liste des substances classées comme stupéfiants
Route of preparation (chemical process)
Route of production: (9S)-HHC does not arise from a direct plant biosynthesis. It forms by catalytic hydrogenation of a tetrahydrocannabinol-type precursor cannabinoid. This reduction creates a new stereogenic centre at C9, producing both the 9R and 9S epimers simultaneously in varying proportions; (9S)-HHC is the systematic by-product of (9R)-HHC in marketed HHC.
Legal framework
France
In France, hexahydrocannabinol and its stereoisomers are classified as narcotics (HHC has featured on the narcotics list since 2023). Sharing the benzo[c]chromene ring of Δ9-THC, (9S)-HHC falls under the regime for hydrogenated derivatives covered by the generic clause of the ANSM Decision of 22 May 2024. Its sale and possession are prohibited.
European Union
At European Union level, HHC is monitored by the EUDA (formerly the EMCDDA) as an emerging semi-synthetic cannabinoid. Several Member States have classified it; status may vary from one country to another.
Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.
Structural classification
- Class
- Semi-synthetic cannabinoid
- Origin
- semisynthetic
- Status
- Narcotic: generic clause
Cannabinoïde semi-synthétique de type dibenzopyrane (benzo[c]chromène), épimère 9S de l'hexahydrocannabinol. Le carbone C9 porte un méthyle en configuration S ; l'anneau cyclohexane hydrogéné, contrairement au Δ9-THC, ne comporte plus de double liaison, ce qui confère au HHC sa stabilité chimique.
Pharmacokinetics
En tant que molécule lipophile de la famille du HHC, le (9S)-HHC suit une distribution tissulaire proche de celle du Δ9-THC. Les données pharmacocinétiques humaines propres à cet épimère isolé restent toutefois non caractérisées.
Metabolism
Comme les autres hexahydrocannabinols, un métabolisme hépatique via les cytochromes P450 est attendu. Les voies métaboliques et métabolites spécifiques du (9S)-HHC ne sont pas documentés séparément dans la littérature.
Toxicology and risks
Le profil toxicologique du (9S)-HHC isolé chez l'humain n'est pas caractérisé. En tant que cannabinoïde semi-synthétique récent, il n'a pas fait l'objet d'études de sécurité dédiées.
Detection and analysis
Les méthodes chromatographiques (LC-MS/MS, GC-MS) permettent de distinguer les épimères 9R et 9S du HHC dans les produits ; leur séparation analytique est un enjeu documenté du contrôle qualité du HHC vendu.
References
- 1.Synthesis and pharmacological activity of the epimers of hexahydrocannabinol (HHC), Scientific Reports 2023DOI 10.1038/s41598-023-38188-5
- 2.Origin of the Different Binding Affinities of (9R)- and (9S)-Hexahydrocannabinol (HHC) for the CB1 and CB2 Cannabinoid Receptors, ACS Chemical Biology 2025PMID 40704858
- 3.In vitro activation of the CB1 receptor by the semi-synthetic cannabinoids HHC, HHC-O and HHC-P, Drug Testing and Analysis 2025PMID 38894658
- 4.PubChem CID 14378541 : 9S-HHC (identifiers)
- 5.Décision ANSM du 22 mai 2024 portant modification de la liste des substances classées comme stupéfiants
Structured data
- InChIKey
- XKRHRBJLCLXSGE-USXIJHARSA-N
- SMILES
- CCCCCC1=CC(=C2[C@@H]3C[C@H](CC[C@H]3C(OC2=C1)(C)C)C)O
- Formula
- C21H32O2
- Molar mass
- 316.50 g·mol⁻¹
- CAS
- 36403-91-5
- PubChem CID
- 14378541
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.