OL-135.

OL-135 is not a cannabinoid. It is a reversible, competitive inhibitor of FAAH, the enzyme that breaks down anandamide and other fatty acid amides. Its electrophilic carbonyl is captured by the catalytic serine Ser241 as a deprotonated hemiketal, a reversible covalent bond seen by crystallography with a humanised FAAH (Mileni et al. 2009). In rodents, it inhibits FAAH in vivo, raising brain anandamide about threefold and producing CB1-dependent antinociceptive effects (Lichtman et al. 2004; Boger et al. 2005; review by Blankman and Cravatt 2013), without hypomotility, catalepsy or hypothermia, but with a short duration of action, under 4 hours. In mice, it decreased allodynia in a chronic constriction injury model of the sciatic nerve, an effect blocked by CB1 or CB2 antagonists but not by capsazepine or naltrexone (Kinsey et al. 2009), and it produced a CB1-dependent analgesic effect in a visceral nociception model (Naidu et al. 2009). In rats, 5.6 and 10 mg/kg disrupted the acquisition of contextual, but not auditory, conditioned fear (Burman et al. 2016). Its selectivity is limited: activity-based profiling ranked it among FAAH inhibitors with several off-targets, including carboxylesterases (Zhang et al. 2007). All these data are preclinical.

Source

A synthetic molecule of the α-ketooxazole class, from the FAAH inhibitor chemistry of Dale L. Boger's laboratory (Scripps Research Institute), absent from cannabis and from any living organism. A research reagent.

No known biological pathway: a synthetic molecule of the α-ketoheterocycle class, unrelated to the biosynthetic pathway of plant cannabinoids.

European Union

A laboratory reagent; no European Union classification specific to the molecule was found in the sources consulted. Its status depends on the national law of each Member State.

France

Not classified: absent from the ANSM list of narcotics (consolidated version updated 16/02/2026). An α-ketooxazole without an indole, indazole or benzo[c]chromene nucleus, it falls under none of the generic entries of Annex IV. The absence of classification is not a marketing authorisation.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Family

ECS pharmacological tool › Enzyme inhibitor

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

No dedicated article.

1. 1Lichtman AH et al., Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity, J Pharmacol Exp Ther 2004 (new tab)PMID 15229230
2. 2Boger DL et al., Discovery of a potent, selective, and efficacious class of reversible α-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics, J Med Chem 2005 (new tab)PMID 15771430
3. 3Mileni M et al., Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by α-ketoheterocycle inhibitors revealed from cocrystal structures, J Am Chem Soc 2009 (new tab)PMID 19722626
4. 4Zhang D et al., Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets, Neuropharmacology 2007 (new tab)PMID 17217969
5. 5Kinsey SG et al., Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain, J Pharmacol Exp Ther 2009 (new tab)PMID 19502530
6. 6Naidu PS et al., Synergy between enzyme inhibitors of fatty acid amide hydrolase and cyclooxygenase in visceral nociception, J Pharmacol Exp Ther 2009 (new tab)PMID 19118134
7. 7Burman MA et al., FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats, Behav Brain Res 2016 (new tab)PMID 27083303
8. 8Blankman JL, Cravatt BF, Chemical probes of endocannabinoid metabolism, Pharmacol Rev 2013 (new tab)PMID 23512546
9. 9Otrubova K, Boger DL, α-Ketoheterocycle-based inhibitors of fatty acid amide hydrolase (FAAH), ACS Chem Neurosci 2012 (new tab)PMID 22639704
10. 10ANSM, Consolidated list of substances classified as narcotics, updated 16 February 2026, annex IV (new tab)
11. 11PubChem, CID 10427006 (OL-135) (new tab)

SMILES

C1=CC=C(C=C1)CCCCCCC(=O)C2=NC=C(O2)C3=CC=CC=N3

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.