In vivo evaluation of synthetic cannabinoid JWH-018 derivatives as potential new psychoactive substances
Salman Khan, Minseo Baek, Jeong-Hoon Jang, In-Soo Myeong
Scientific Reports May 11, 2026 DOI: 10.1038/s41598-026-51639-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Not stated (likely laboratory animals, but not specified in the text) |
| Interventions | JWH-018-5-OMe JWH-018-6-OMe |
| Key points | JWH-018-5-OMe selectively reduced rectal temperature, while JWH-018-6-OMe produced robust, dose-dependent effects across catalepsy, hypothermia, analgesia, and locomotor activity, resembling the parent compound JWH-018. These results demonstrate that substitution position on the indole scaffold influences psychoactive effects. |
Abstract
Synthetic cannabinoid receptor agonists constitute a prominent class of new psychoactive substances (NPS), in which minor structural modifications can markedly influence in vivo pharmacological outcomes. In this study, methoxy-substituted derivatives of JWH-018 were synthesized to examine the effect of substitution position on behavioral activity. JWH-018–5-OMe and JWH-018–6-OMe were evaluated using four in vivo assays, including catalepsy, hypothermia, analgesia, and locomotor activity. JWH-018–5-OMe selectively reduced rectal temperature, with limited effects observed in catalepsy, analgesia, and locomotor activity. Notably, JWH-018–6-OMe elicited robust and dose-dependent effects across all four behavioral endpoints, closely resembling the pharmacological profile of the parent compound, JWH-018. Collectively, these results demonstrate that structural variations on the indole scaffold can produce measurable psychoactive effects, underscoring the importance of continued evaluation of indole-based synthetic cannabinoids within the NPS framework.