UR-144

UR-144 is a synthetic cannabinoid in the tetramethylcyclopropylindole family. It was developed as a cannabinoid research compound and later appeared in herbal smoking mixtures. Laboratory studies show that UR-144 is a full agonist at CB₁ and CB₂ receptors, with THC-like effects in animal models. It has been associated with acute intoxications, including altered mental status and kidney injury, although clinical cases often involve other substances.

Chemistry and history

UR-144 is (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone. Its structure contains an indole core, a pentyl chain attached to the indole nitrogen and a tetramethylcyclopropyl ketone group. It is the non-fluorinated counterpart of XLR-11.

UR-144 was identified in confiscated products in the early 2010s and became a common ingredient in some synthetic cannabis mixtures. UNODC lists it among the cyclopropoylindole synthetic cannabinoid receptor agonists (UNODC recommended methods for synthetic cannabinoid analysis).

Pharmacology

UR-144 has low-nanomolar affinity for CB₁ and CB₂ receptors and acts as a full agonist in the assays reported. In mice, it produced dose-dependent antinociception, hypothermia, catalepsy and suppression of locomotor activity. These effects were blocked by a CB₁ antagonist, supporting a cannabinoid receptor-mediated mechanism (Wiley and colleagues, 2013).

The same study found that UR-144 substituted for THC in a drug-discrimination procedure in mice. This supports THC-like pharmacological activity, without directly establishing its subjective effects in humans.

Metabolism

UR-144 undergoes extensive metabolism, including oxidation of the tetramethylcyclopropyl group and formation of hydroxylated and carboxylated products. Human liver enzyme studies identified CYP3A4 as the main contributor to metabolism, with smaller contributions from CYP1A2 and CYP2C19 (CYP450-mediated metabolism of UR-144 and XLR-11, 2015).

Urinary metabolites are often more useful for forensic confirmation than the parent compound. The metabolism study found extensive phase I and phase II transformations, with glucuronide conjugates among the major urinary products.

Reported effects and clinical findings

Products containing UR-144 have been associated with acute synthetic cannabinoid intoxication. Reported presentations across the group include altered mental status, agitation, confusion, drowsiness and cardiovascular changes. A retrospective clinical review of synthetic cannabinoid cases found UR-144 among the compounds identified in toxicological samples, but co-exposure and variable product composition limited compound-specific conclusions (Post-mortem toxicology review of synthetic cannabinoid receptor agonists, 2020).

Toxicity and research limitations

UR-144 has a documented forensic presence and a well-described animal pharmacological profile, but controlled human studies are lacking. The acute toxic range, dependence potential and long-term effects have not been established. Clinical reports involving herbal mixtures should be interpreted cautiously because more than one synthetic cannabinoid may be present.

Related compounds

UR-144 is related to XLR-11, XLR-12 and other tetramethylcyclopropylindoles. XLR-11 is its 5-fluoropentyl analogue, while XLR-12 carries a 4,4,4-trifluorobutyl chain.