AM-2389
Full and highly potent agonist of the CB1 receptor, a laboratory tool with no human data at all.
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.
C₂₅H₃₈O₃
CAS 1256842-49-5
- Family
- Synthetic CB receptor agonistResearch ligand or medicine
- Molar mass
- 386.60 g/mol
Updated on
In plain terms
AM-2389 is a laboratory molecule, made entirely by synthesis: it does not exist in hemp. It binds to the same brain receptor as THC, but far more strongly, and in animals its effects set in slowly and then last a very long time. No study in humans was found, and it has no place in a consumer product.
Receptors and activity
Target network
- Activates
- Binds or modulates
The lower the cited value, the closer the target sits to AM-2389: one ring per factor of 100. A target with no measured value stays on the edge.
Where these targets live
Where each target has been found in humans, according to the cited studies. The map shows the target, not an effect of AM-2389.
CB1CB1 found in 7 regions of the body
- Basal gangliadenseMost dense in basal ganglia outflow nuclei1
- CerebellumdenseVery dense in the cerebellum1
- HippocampusdenseVery high concentrations in the hippocampus2
- AmygdaladenseHigh concentrations in the amygdala2
- CortexpresentPresent throughout the neocortex2
- Adipose tissuepresentExpressed in adipose tissue3
- GutpresentColonic epithelium, smooth muscle and plexus4
Map sources
- Herkenham M et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A, 1990 (new tab)
- Glass M et al. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience, 1997 (new tab)
- Engeli S et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005 (new tab)
- Wright K et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 2005 (new tab)
Cited values
- CB1AgonistKi = 0.2 nM · rat97 out of 100
Nikas et al. 2010, J Med Chem (new tab) · [3H]CP-55,940 displacement, rat brain membranes; EC50 1.5 nM for inhibition of forskolin-stimulated cAMP (full agonist)
- CB2Binding (function not established)Ki = 4.2 nM · mouse73 out of 100
Nikas et al. 2010, J Med Chem (new tab) · [3H]CP-55,940 displacement, mouse spleen membranes; 5.13 nM at human CB2 (HEK293); efficacy not reported
Pharmacology
AM-2389 is a synthetic classical cannabinoid: a hexahydrocannabinol hydroxylated at position 9 whose side chain carries a 1-hexylcyclobutyl group. This modification gives it a very high affinity for the CB1 receptor (0.16 nM on rat brain membranes), with a preference of about 26-fold for CB1 over mouse CB2 (Nikas et al., 2010). In a functional test, the molecule behaves as a full agonist of the CB1 receptor, where THC is only a partial agonist. In the rat, in a discrimination test in which animals distinguish the cannabinergic AM5983 from vehicle, AM-2389 is about a hundred times more potent than Δ9-THC (median effective dose of 0.0025 against 0.2635 mg/kg), and the estimated functional half-life of its effects is about seventeen hours; in mice, its hypothermic effect sets in slowly and extends well beyond that of THC (Järbe et al., 2012). The published work uses it for precisely this: to maintain a sustained activation of the endocannabinoid system in rodents and monkeys, then to study tolerance, dependence and withdrawal. Its action at TRPV1, GPR55, PPARγ or 5-HT1A was not evaluated in the sources consulted, and human data are entirely lacking.
Key sources.
- Nikas SP et al. Novel 1',1'-chain substituted hexahydrocannabinols: 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid receptor 1 (CB1) agonist. J Med Chem 2010;53(19):6996-7010 (new tab)PMID 20925434
- Järbe TU et al. AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice. Psychopharmacology 2012;220(2):417-26 (new tab)PMID 21989802
- Paronis CA et al. Δ9-tetrahydrocannabinol acts as a partial agonist/antagonist in mice. Behav Pharmacol 2012 (new tab)PMID 23075707
- Paronis CA et al. Diuretic effects of cannabinoids. J Pharmacol Exp Ther 2013 (new tab)PMID 23019138
- Tai S et al. Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist. Psychopharmacology 2015 (new tab)PMID 25772338
- Kangas BD et al. Cannabinoid antagonist drug discrimination in nonhuman primates. J Pharmacol Exp Ther 2020 (new tab)PMID 31641018
- Paronis C et al. Evidence for spontaneous cannabinoid withdrawal in mice. Behav Pharmacol 2022 (new tab)PMID 35288509
- Missig G et al. Altered sleep during spontaneous cannabinoid withdrawal in male mice. Behav Pharmacol 2022 (new tab)PMID 35288510
- Kohut SJ et al. Effects of cannabinoid exposure on short-term memory and medial orbitofrontal cortex function and chemistry in adolescent female rhesus macaques. Front Neurosci 2022 (new tab)PMID 36248648
- Zangani C et al. The e-Psychonauts' 'Spiced' World: assessment of the synthetic cannabinoids' information available online. Curr Neuropharmacol 2020 (AM-2389 absent from the UNODC and EUDA lists, present in NPSFinder) (new tab)PMID 32116194
- ANSM, consolidated list of substances classified as narcotics, updated 16 February 2026 (AM-2389 not named; HHC, HHC-acetate and HHCP named; benzo[c]chromene derivatives family in annex IV) (new tab)
- PubChem CID 49783410, AM-2389 (names, identifiers) (new tab)
History
- Source
- An entirely synthetic molecule, absent from cannabis and from any living organism: it was designed in medicinal chemistry from the skeleton of the classical cannabinoids. According to the literature consulted, it is used as a laboratory research tool. It appears neither in the lists of the EUDA and of UNODC recording the synthetic cannabinoids reported, nor, as far as the sources consulted show, in seized products (Zangani et al., 2020).
Origin
Laboratory synthesis
No biological pathway: the molecule comes from no enzyme, plant or animal. It belongs solely to synthetic chemistry, in the series of the classical cannabinoids (hexahydrocannabinols), with a saturated carbon ring and a hydroxyl at position 9 in the beta configuration.
Legal framework
- European Union
The substance is not listed in the Annex to Council Framework Decision 2004/757/JHA (consolidated version of 12 January 2026), which lists the new psychoactive substances controlled at European Union level; control is a matter for national law. It appears neither in the lists of the EUDA nor in those of UNODC recording the synthetic cannabinoids reported (Zangani et al., 2020). It does not appear in the schedules of the 1971 Convention on Psychotropic Substances (green list of the INCB, 35th and 36th editions).
- France
AM-2389 is named in no entry of the consolidated ANSM list (updated 16 February 2026). The entry « Tétrahydrocannabinols, leurs esters, éthers, sels », placed in annex III since the decision of 6 February 2026, covers tetrahydrocannabinols and their derivatives: AM-2389 is a hexahydrocannabinol, whose carbon ring is saturated, and not an ester, ether or salt of a tetrahydrocannabinol. HHC, its acetate (HHC-O) and hexahydrocannabiphorol (HHCP) are named in the list by decisions of 12 June 2023, not this compound. The generic family of annex IV introduced by the ANSM decisions of 22 May and 3 June 2024 (derivatives of the benzo[c]chromene nucleus, hydrogenated or not on ring A) enumerates the substituents allowed at positions 1, 3, 6 and 9; AM-2389 meets these criteria at positions 1, 3 and 6, but carries a direct hydroxyl at position 9 (ketone, alkyl, hydroxyalkyl or alkoxy in the text), so its attachment to this family is not established. It is therefore not classified by name; its coverage by the generic clause remains to be confirmed by the ANSM or a lawyer. This does not make it an authorised product: no food, cosmetic or medicinal use is recognised.
Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.
Classification
Family, origin and source verification
- Family
Synthetic CB receptor agonist › Research ligand or medicine
- Class
classical
- Verification
Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.
- Wikipedia (English)
Article paired by the molecule's structure (InChIKey), revision read on 19 October 2026. Read as a second opinion, never cited as a source.
References
- Nikas SP et al. Novel 1',1'-chain substituted hexahydrocannabinols: 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid receptor 1 (CB1) agonist. J Med Chem 2010;53(19):6996-7010 (new tab)PMID 20925434
- Järbe TU et al. AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice. Psychopharmacology 2012;220(2):417-26 (new tab)PMID 21989802
- Paronis CA et al. Δ9-tetrahydrocannabinol acts as a partial agonist/antagonist in mice. Behav Pharmacol 2012 (new tab)PMID 23075707
- Paronis CA et al. Diuretic effects of cannabinoids. J Pharmacol Exp Ther 2013 (new tab)PMID 23019138
- Tai S et al. Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist. Psychopharmacology 2015 (new tab)PMID 25772338
- Kangas BD et al. Cannabinoid antagonist drug discrimination in nonhuman primates. J Pharmacol Exp Ther 2020 (new tab)PMID 31641018
- Paronis C et al. Evidence for spontaneous cannabinoid withdrawal in mice. Behav Pharmacol 2022 (new tab)PMID 35288509
- Missig G et al. Altered sleep during spontaneous cannabinoid withdrawal in male mice. Behav Pharmacol 2022 (new tab)PMID 35288510
- Kohut SJ et al. Effects of cannabinoid exposure on short-term memory and medial orbitofrontal cortex function and chemistry in adolescent female rhesus macaques. Front Neurosci 2022 (new tab)PMID 36248648
- Zangani C et al. The e-Psychonauts' 'Spiced' World: assessment of the synthetic cannabinoids' information available online. Curr Neuropharmacol 2020 (AM-2389 absent from the UNODC and EUDA lists, present in NPSFinder) (new tab)PMID 32116194
- ANSM, consolidated list of substances classified as narcotics, updated 16 February 2026 (AM-2389 not named; HHC, HHC-acetate and HHCP named; benzo[c]chromene derivatives family in annex IV) (new tab)
- PubChem CID 49783410, AM-2389 (names, identifiers) (new tab)
Identifiers
Names
- IUPAC name
- (6aR,9R,10aR)-3-(1-hexylcyclobutyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromene-1,9-diol
- Other names
- AM2389 · 9β-hydroxy-3-(1-hexylcyclobut-1-yl)-hexahydrocannabinol · (6aR,9R,10aR)-3-(1-hexylcyclobutyl)-6a,7,8,9,10,10a-hexahydro-6,6-dimethyl-6H-dibenzo[b,d]pyran-1,9-diol
Identifiers
- Formula
- C₂₅H₃₈O₃
- CAS
- 1256842-49-5
- PubChem CID
- 49783410(new tab)
- InChIKey
- CSXKNESDVLECTJ-VAMGGRTRSA-N
- SMILES
- CCCCCCC1(CCC1)
C2= CC3= C([C@@H] 4C[C@@H] (CC[C@H] 4C(O3) (C) C) O) C(= C2) O
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.