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<p>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 <b>JWH-018</b> were synthesized to examine the effect of substitution position on behavioral activity. <b>JWH-018–5-OMe</b> and <b>JWH-018–6-OMe</b> 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, <b>JWH-018–6-OMe</b> elicited robust and dose-dependent effects across all four behavioral endpoints, closely resembling the pharmacological profile of the parent compound, <b>JWH-018</b>. 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.</p>

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In vivo evaluation of synthetic cannabinoid JWH-018 derivatives as potential new psychoactive substances

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月11日

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  • Salman Khan,
  • Minseo Baek,
  • Jeong-Hoon Jang,
  • In-Soo Myeong

摘要

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.