ZCZ-011
CB1 positive allosteric modulator: in mice, CB1-dependent antinociceptive effect with no cannabimimetic effect of its own.
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.
C₂₁H₁₈N₂O₂S
CAS 1998197-39-9
- Family
- ECS pharmacological toolAllosteric modulator
- Molar mass
- 362.40 g/mol
Updated on
In plain terms
ZCZ-011 is not an ordinary cannabinoid: instead of activating the CB1 receptor itself, it sits alongside and amplifies the signal of molecules the body already makes. In mice, given alone, it did not cause the usual effects of THC, while reducing pain responses in two models. It is a research tool; no study in humans was found.
Receptors and activity
Target network
- Activates
The lower the cited value, the closer the target sits to ZCZ-011: 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 ZCZ-011.
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
- CB1Positive allosteric modulatorno measured value cited
Positive allosteric modulator: potentiates [3H]CP55,940 binding and anandamide-stimulated [35S]GTPγS binding, β-arrestin recruitment and ERK phosphorylation; no effect of its own in the cannabimimetic tests; no numerical value in the abstract (Ignatowska-Jankowska et al. 2015)
Pharmacology
ZCZ-011 illustrates a different strategy from that of CB1 orthosteric agonists. A positive allosteric modulator binds a distinct site and makes the receptor more sensitive to ligands already present, without triggering signalling itself. The 2015 study showed that ZCZ-011 potentiates [3H]CP55,940 binding, enhances anandamide-stimulated GTPγS binding in mouse brain membranes and increases β-arrestin recruitment and ERK phosphorylation in human CB1 cells. In mice, brain penetrant, it increased the potency of orthosteric agonists in antinociception, hypothermia, catalepsy, locomotor activity and discrimination tests; alone, it remained without effect in these tests and produced neither place preference nor aversion, but it produced CB1-mediated antinociceptive effects in neuropathic and inflammatory pain models. The authors see in this a first proof of principle that a CB1 PAM could act in these models with little or no cannabimimetic effects. In a 2024 study in transgenic mice expressing the HIV-1 Tat protein, chronic treatment for 14 days at 10 mg/kg did not change body mass, locomotor activity or anxiety-like behaviour, but increased hot-plate latency and improved motor coordination and recognition memory in females only (Yadav-Samudrala et al. 2024). These results are preclinical; no study in humans was found.
Key sources.
- Ignatowska-Jankowska BM et al. A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects. Neuropsychopharmacology, 2015 (new tab)PMID 26052038
- Yadav-Samudrala BJ et al. Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice. PLoS One, 2024 (new tab)PMID 38913661
- PubChem, ZCZ-011, CID 71819307 (identifiers and properties) (new tab)
History
- Source
- An entirely synthetic molecule, absent from hemp and from any living organism. It is described as a research reagent; no human use or circulation as a consumer product was found in the sources consulted.
Origin
Research tool
No known biosynthetic pathway: ZCZ-011 is produced by no plant or living organism. It is a synthetic compound of the class of 2-phenylindoles bearing a nitroethyl chain substituted by a thiophene.
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 is not listed in the schedules of the 1971 Convention on Psychotropic Substances (INCB Green List, 36th edition, 2025, text reviewed). No marketing authorisation was found.
- France
Not classified: ZCZ-011 is not on the ANSM consolidated list of narcotics (updated 16/02/2026). This 2-phenylindole with an unsubstituted indole nitrogen, and no methanone, carboxamide or carboxylate bridge at position 3, falls within none of the generic indole families of that list, which require a substituent on the indole nitrogen, nor within the benzo[c]chromene clause. No marketing authorisation was found.
Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.
Classification
Family, origin and source verification
- Family
ECS pharmacological tool › Allosteric modulator
- 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
- Ignatowska-Jankowska BM et al. A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects. Neuropsychopharmacology, 2015 (new tab)PMID 26052038
- Yadav-Samudrala BJ et al. Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice. PLoS One, 2024 (new tab)PMID 38913661
- PubChem, ZCZ-011, CID 71819307 (identifiers and properties) (new tab)
Identifiers
Names
- IUPAC name
- 6-methyl-3-(2-nitro-1-thiophen-2-ylethyl)-2-phenyl-1H-indole
- Other names
- ZCZ011 · ZCZ 011
Identifiers
- Formula
- C₂₁H₁₈N₂O₂S
- CAS
- 1998197-39-9
- PubChem CID
- 71819307(new tab)
- InChIKey
- RJSPNRDBWHHFMH-UHFFFAOYSA-N
- SMILES
- CC1=
CC2= C(C= C1) C(= C(N2) C3= CC= CC= C3) C(C[N+] (= O) [O-] ) C4= CC= CS4
LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.