Abstract：
Background: Cannabis and its primary psychoactive constituent delta-9-tetrahydrocannabinol (D9-THC) produce biphasic, dose-dependent effects on anxiety. In addition to D9-THC, cannabis contains other \"minor\" cannabinoids and terpenes with purported therapeutic potential for the treatment of anxiety. Empirical data on potential therapeutic effects of these compounds is limited. The current study evaluated the effects of selected minor cannabinoids and terpenes in a battery of tests sensitive to anxiolytic and anxiogenic drugs. Methods: In Experiment 1, adult male Sprague Dawley rats (N=7-8/group) were administered acute oral doses of one of five minor cannabinoids: delta-8-tetrahydrocannabinol (D8-THC; 10 mg/kg), tetrahydrocannabivarin (32 mg/kg), cannabidiolic acid (32 mg/kg), cannabidivarin (32 mg/kg), and cannabigerol (100 mg/kg), or one of five terpenes: D-limonene (17 mg/kg), ⍺-pinene (100 mg/kg), ⍺-terpineol (10 mg/kg), bisabolol (100 mg/kg), and β-caryophyllene (17 mg/kg), or vehicle (medium-chain triglycerides [MCT] oil). Ethyl alcohol was tested as an active comparator. Thirty minutes post-administration, the marble burying test, the three-chamber social interaction test, and the novelty-induced hypophagia test were completed; motor activity was assessed throughout testing. Experiment 2 examined the potential anxiolytic effects of minor cannabinoids when administered chronically; rats administered MCT oil or minor cannabinoids in Experiment 1 continued receiving once-daily doses for 21 days and were assessed using the same test battery after 7, 14, and 21 days of administration. Results and Conclusions: When compared to vehicle, acute administration of bisabolol and D-limonene increased the amount of food consumed and bisabolol-, D-limonene-, ⍺-pinene-, and β-caryophyllene decreased percent time spent in the outer zone in the novelty-induced hypophagia test, suggestive of an anxiolytic effect. Only ethanol increased social interaction. After acute administration, anxiogenic effects in the marble burying test were observed for D8-THC, but not for other minor cannabinoids and terpenes. Throughout chronic administration, only D8-THC displayed anxiogenic effects in the novelty-induced hypophagia test. The other cannabinoids did not show anxiolytic or anxiogenic effects in any of the tests at the doses or times tested. The minor cannabinoids and terpenes did not impair or stimulate general motor activity. These data provide a foundation for future studies investigating cannabinoid/terpene interactions.
摘要：
背景：大麻及其主要的精神活性成分δ-9-四氢大麻酚（D9-THC）产生双相，对焦虑的剂量依赖效应。除了D9-THC，大麻含有其他“次要”大麻素和萜烯，具有治疗焦虑症的治疗潜力。关于这些化合物的潜在治疗效果的经验数据是有限的。目前的研究评估了选定的次要大麻素和萜烯在一系列对抗焦虑和抗焦虑药物敏感的测试中的作用。方法：在实验1中，成年雄性SpragueDawley大鼠（N=7-8/组）给予急性口服剂量的五种次要大麻素之一：δ-8-四氢大麻酚（D8-THC；10mg/kg），四氢大麻酚(32mg/kg),大麻酚酸（32毫克/千克），大麻素（32毫克/千克），和大麻酚（100毫克/千克），或五种萜烯之一：D-柠檬烯（17mg/kg），3-pine烯（100mg/kg），-松油醇（10mg/kg），没药醇（100mg/kg），和β-石竹烯（17毫克/千克），或载体（中链甘油三酯[MCT]油）。测试乙醇作为活性比较物。给药后30分钟,大理石掩埋试验,三室社交互动测试，并完成了新颖性诱导的低吞咽测试；在整个测试过程中评估了运动活动。实验2检查了慢性施用时次要大麻素的潜在抗焦虑作用；在实验1中施用MCT油或次要大麻素的大鼠继续接受每日一次剂量21天，并在施用7、14和21天后使用相同的测试电池进行评估。结果与结论：与车辆相比，急性服用没药醇和D-柠檬烯增加了食物的消耗量和没药醇-，D-柠檬烯-,-派恩-,和β-石竹烯减少了在外部区域花费的时间百分比，在新颖性诱导的低吞下试验，暗示有抗焦虑作用.只有乙醇增加了社会互动。急性给药后，在大理石掩埋试验中观察到D8-THC的抗焦虑作用，但不适用于其他次要大麻素和萜烯。在整个长期给药过程中，只有D8-THC在新颖性食欲不振试验中表现出焦虑作用。其他大麻素在测试的剂量或时间的任何测试中都没有显示抗焦虑或抗焦虑作用。次要大麻素和萜烯不会损害或刺激一般运动活动。这些数据为研究大麻素/萜烯相互作用的未来研究提供了基础。
