JWH-015 is a chemical from the naphthoylindole family that acts as a subtype-selective cannabinoid agonist. Its affinity for CB<sub>2</sub> receptors is 13.8 nM, while its affinity for CB<sub>1</sub> is 383 nM, meaning that it binds almost 28 times more strongly to CB<sub>2</sub> than to CB<sub>1</sub>. However, it still displays some CB<sub>1</sub> activity, and in some model systems can be very potent and efficacious at activating CB<sub>1</sub> receptors, and therefore it is not as selective as newer drugs such as JWH-133. It has been shown to possess immunomodulatory effects, and CB<sub>2</sub> agonists may be useful in the treatment of pain and inflammation. It was discovered and named after John W. Huffman.
JWH-015 has been shown in vitro to be metabolized primarily by hydroxylation and N-dealkylation, and also by epoxidation of the naphthalene ring, similar to the metabolic pathways seen for other aminoalkylindole cannabinoids such as WIN 55,212-2. Epoxidation of polycyclic aromatic hydrocarbons (see for example benzo(a)pyrene toxicity) can produce carcinogenic metabolites, although there is no evidence to show that JWH-015 or other aminoalkylindole cannabinoids are actually carcinogenic in vivo. JWH-015 may signal certain cancers to shrink through a process called apoptosis.
In the United States, all CB<sub>1</sub> receptor agonists of the 3-(1-naphthoyl)indole class such as JWH-015 are Schedule I Controlled Substances.
As of October 2015 JWH-015 is a controlled substance in China.
JWH-015 has been classified under the German BtMG as Anlage II.