Kayir Hakan, Kouroukis Larissa, Aziz Iman, Khokhar Jibran Younis
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
Biomolecules. 2025 Sep 18;15(9):1329. doi: 10.3390/biom15091329.
Delta-9-Tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid and structural analog of THC, exhibits a dual pharmacological profile as a CB1 receptor agonist/antagonist and a partial CB2 agonist. This study evaluated the effects of THCV in a THC discrimination model in rats. Male Sprague-Dawley rats ( = 16, 300-340 g, PND60) were trained under a fixed ratio 20 (FR20) schedule to discriminate THC (3 mg/kg) from vehicle. Substitution tests were conducted with THC (0.325-3 mg/kg), THCV (0.75-6 mg/kg), and THC-THCV combinations. THCV produced an inverted U-shaped substitution curve, significantly differing from vehicle ( = 0.008). At 3 mg/kg, THCV partially substituted for THC (54.6% ± 17.82, = 0.003). Response rate significantly increased during the substitution test with 3 mg/kg of THCV ( = 0.042). THCV (6 mg/kg) reversed THC (0.75 mg/kg)-induced responding ( = 0.040), with no significant change in response rate ( = 0.247). However, THCV combined with THC (1.5 mg/kg) affected response rates ( = 0.012), with 6 mg/kg significantly reducing rates vs. 3 mg/kg ( = 0.013). Blood THC and 11-OH-THC levels remained unchanged when THC was combined with THCV. The findings suggest THCV can partially mimic or block THC's discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist.
Δ⁹-四氢大麻二酚（THCV）是一种天然存在的大麻素，也是四氢大麻酚（THC）的结构类似物，具有作为CB1受体激动剂/拮抗剂和部分CB2激动剂的双重药理特性。本研究评估了THCV在大鼠THC辨别模型中的作用。雄性斯普拉格-道利大鼠（n = 16，体重300 - 340克，出生后第60天）在固定比例20（FR20）的训练方案下接受训练，以区分THC（3毫克/千克）和赋形剂。用THC（0.325 - 3毫克/千克）、THCV（0.75 - 6毫克/千克）以及THC - THCV组合进行替代试验。THCV产生了一条倒U形的替代曲线，与赋形剂有显著差异（P = 0.008）。在3毫克/千克剂量下，THCV部分替代了THC（54.6% ± 17.82，P = 0.003）。在使用3毫克/千克THCV进行替代试验期间，反应率显著增加（P = 0.042）。THCV（6毫克/千克）逆转了THC（0.75毫克/千克）诱导的反应（P = 0.040），反应率无显著变化（P = 0.247）。然而，THCV与THC（1.5毫克/千克）联合使用影响了反应率（P = 0.012），6毫克/千克剂量组与3毫克/千克剂量组相比，反应率显著降低（P = 0.013）。当THC与THCV联合使用时，血液中THC和11 - 羟基 - THC水平保持不变。研究结果表明，THCV可以剂量依赖性方式部分模拟或阻断THC的辨别效应，可能作为一种部分CB1激动剂发挥作用。
