JWH-398 is an analgesic compound belonging to the naphthoylindole family, functioning as a cannabinoid agonist with activity at both the CB1 and CB2 receptors. It exhibits mild selectivity for CB1, demonstrating a Ki of 2.3 nM while registering 2.8 nM at CB2 receptors. The EMCDDA identified this synthetic chemical as an ingredient in three distinct “herbal incense” products acquired from online shops between February and June 2009. The compound’s discovery is credited to John W. Huffman, whom it is named after.
In the United States, JWH-398 is categorized as a Schedule I controlled substance.

IUPAC name
CAS Number1292765-18-4 
CompTox Dashboard (EPA)DTXSID40156131
Chemical and physical data
Molar mass375.90 g·mol−1


1. What is JWH-398?

JWH-398 is a synthetic compound from the naphthoylindole family, known for its analgesic properties. It acts as a cannabinoid agonist, affecting the CB1 and CB2 receptors.

2. How does JWH-398 interact with cannabinoid receptors?

JWH-398 binds to cannabinoid receptors, specifically the CB1 and CB2 receptors. This interaction influences various physiological and psychological processes.

3. Is JWH-398 selective for a specific cannabinoid receptor?

JWH-398 exhibits mild selectivity for the CB1 receptor with a Ki (binding affinity) of 2.3 nM and registers a Ki of 2.8 nM at CB2 receptors. This indicates a slight preference for CB1, but it interacts with both receptor types.

4. What is the history of JWH-398’s discovery?

John W. Huffman, a prominent figure in cannabinoid research, discovered JWH-398. The compound bears his name in recognition of his contributions to this field.

5. Where was JWH-398 found in 2009?

In 2009, JWH-398 was identified as an ingredient in three “herbal incense” products purchased from online shops. This discovery raised awareness about its presence in certain products.

6. What is the legal status of JWH-398 in the United States?

In the United States, JWH-398 is classified as a Schedule I controlled substance. This categorization places it under strict legal control due to its potential misuse and abuse.

7. Are there potential medical applications for JWH-398?

While JWH-398’s cannabinoid properties suggest possible medical applications, its regulatory status and potential risks associated with synthetic compounds have limited its exploration in the medical field. Researchers and authorities prioritize safety in the evaluation of such substances.


  1. Amendments to Latvian Regulations (2005): Grozījumi Ministru kabineta 2005.gada 8.novembra noteikumos Nr.847 “Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem” highlight changes made to Latvian regulations regarding controlled substances, including narkotiskajām vielām, psihotropajām vielām, and prekursoriem.
  2. Insights into Cannabinoid Receptors (2009): Huffman JW’s research, detailed in Reggio PH’s “Cannabimimetic Indoles, Pyrroles, and Indenes: Structure–Activity Relationships and Receptor Interactions,” provides valuable insights into cannabinoid receptors. This work explores the relationships between structure and activity, shedding light on receptor interactions.
  3. Understanding the ‘Spice’ Phenomenon (November 2009): A report from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) titled “Understanding the ‘Spice’ phenomenon” delves into the phenomenon of synthetic cannabinoids, often marketed as ‘Spice.’ This report, released in November 2009, offers crucial insights into these substances.
  4. Structure-Activity Relationships in Cannabinoid Research (2009): Huffman JW and colleagues examined the structure-activity relationships at the CB1 and CB2 receptors for 1-Alkyl-3-(1-Naphthoyl-4 and 8-Halogen Substituted) Indoles. Their findings were presented at the 19th Annual Symposium on the Cannabinoids held in Burlington, Vermont.
  5. Controlled Substances Regulated by the DEA: The Drug Enforcement Administration (DEA) maintains a list of controlled substances, reflecting the legal framework for regulating these substances in the United States. This list is essential for understanding the controlled status of various compounds and substances.

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