Cannabinoids have been proposed as therapeutics for pain mitigation. Therefore, the antihyperalgesic effects of a proprietary cannabis-derived mixture, Non-Euphoric Phytocannabinoid Elixir #14 (NEPE14), were examined in a persistent Complete Freund's Adjuvant (CFA)-induced model of inflammatory pain. The acute antinociceptive and operant behavioral effects of NEPE14 were then compared with single cannabinoid preparations of Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-THC, the synthetic cannabinoid (−)-CP 55,940 (CP), and cannabidiol (CBD). The THC isomers and CP were also administered with cannabinoid-type-1 receptor (CB1R) antagonist, AM251, and NEPE14 was administered in combination with THC or CP. To induce inflammation, CFA or saline was administered into the paw of male and female Wistar rats. After injections, mechanical hypersensitivity was assessed with Von Frey filaments, and thermal hyperalgesia with a thermal probe. Nine Sprague Dawley rats were also trained to respond under a fixed-ratio 30 schedule for food reinforcers during a 60-min session. Response rates were recorded during the session and warm-water tail-withdrawal latency post session. In CFA-administered rats, mechanical and thermal paw-withdrawal thresholds significantly decreased compared to vehicle, indicating hyperalgesia. Both i.p. (6.6–20.7 ml/kg) and o.m. (30–300 μL) NEPE14 significantly reduced the mechanical and thermal hyperalgesia. In contrast, neither NEPE14 (3.7–20.7 mL/kg i.p., 100–1000 μL o.m.) nor CBD (10–100 mg/kg) significantly decreased response rates or increased tail-withdrawal latency. Acute Δ9-THC, Δ8-THC (1–5.6 mg/kg), and CP (0.032–0.18 mg/kg) significantly and dose-dependently decreased overall response rate and increased tail-withdrawal latency compared to vehicle. AM251 significantly antagonized the rate-decreasing effects of THC, and CP, as well as the antinociceptive effects of CP. Combinations of NEPE14 with Δ9-THC or CP were not significantly different from these cannabinoids alone. In summary, while NEPE14 significantly reduced CFA-induced hyperalgesia, it was more similar to CBD than Δ9-THC, Δ8-THC, and CP for significantly reducing thermal nociception and disrupting conditioned behavior.

大麻素已被提议作为缓解疼痛的疗法。因此，在持续性完全弗氏佐剂(CFA) 诱导的炎性疼痛模型中检查了专有的大麻衍生混合物非欣快植物大麻素 Elixir #14 (NEPE14) 的抗痛觉过敏作用。然后将 NEPE14 的急性镇痛和操作行为作用与 Δ9-四氢大麻酚 (Δ9-THC)、Δ8-THC、合成大麻素 (−)-CP 55,940 (CP) 和大麻二酚(CBD) 的单一大麻素制剂进行比较。THC异构体和CP还与大麻素1型受体(CB1R)拮抗剂AM251一起施用，并且NEPE14与THC或CP组合施用。为了诱发炎症，将 CFA 或盐水注射到雄性和雌性 Wistar 大鼠的爪子中。注射后，用冯弗雷丝评估机械过敏，并用热探针评估热痛觉过敏。9 只Sprague Dawley 大鼠还接受了训练，在 60 分钟的训练中按照固定比例 30 的食物强化剂时间表做出反应。记录治疗期间的反应率和治疗后的温水尾缩潜伏期。在给予 CFA 的大鼠中，与媒介物相比，机械和热缩爪阈值显着降低，表明痛觉过敏。ip (6.6–20.7 ml/kg) 和om (30–300 μL) NEPE14 均显着降低机械和热痛觉过敏。相比之下，NEPE14（3.7-20.7 mL/kg ip，100-1000 μL om）和 CBD（10-100 mg/kg）均未显着降低反应率或增加尾部撤回潜伏期。与赋形剂相比，急性 Δ9-THC、Δ8-THC (1–5.6 mg/kg) 和 CP (0.032–0.18 mg/kg) 显着且剂量依赖性地降低总体反应率并增加尾部撤回潜伏期。AM251 显着拮抗 THC 和 CP 的降速作用以及 CP 的抗伤害作用。NEPE14 与 Δ9-THC 或 CP 的组合与单独使用这些大麻素没有显着差异。总之，虽然 NEPE14 显着减少了 CFA 引起的痛觉过敏，但它在显着减少热伤害感受和破坏条件行为方面与 CBD 比 Δ9-THC、Δ8-THC 和 CP 更相似。