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Cannabis Extract CT-921 Has a High Efficacy-Adverse Effect Profile in a Neuropathic Pain Model.
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-08-17 , DOI: 10.2147/dddt.s247584 Elham Rouhollahi 1 , Bernard A MacLeod 1 , Alasdair M Barr 1 , Ernest Puil 1
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-08-17 , DOI: 10.2147/dddt.s247584 Elham Rouhollahi 1 , Bernard A MacLeod 1 , Alasdair M Barr 1 , Ernest Puil 1
Affiliation
Background: Legalization of cannabis encourages the development of specific cultivars to treat disease such as neuropathic pain. Because of the large number of cultivars, it is necessary to prioritize extracts before proceeding to clinical trials.
Purpose: To compare extracts of two unique cannabis cultivars (CT-921, CT-928) for treatment of neuropathic pain induced by constriction of sciatic nerve in mice and to illustrate the use of this animal model to set priority for future trials.
Methods: Pain severity was measured by threshold force causing paw withdrawal. Dose–response relationships and time course were determined for intravenously injected extracts of cultivars and vehicle. The doses for allodynia relief were correlated with decreased respiratory rate, temperature and behavioral changes.
Results: Effective analgesic dose for 50 and 95% (ED50An and ED95An) was 15, and 29 mg/kg for CT-921 and 0.9 and 4.7 for CT-928. At ED50An, for both extracts, the duration was 120 min. At ED95An, administration of CT-928 significantly decreased respiratory rate while CT-921 did not. CT-928 decreased temperature more than CT-921. CT-928 produced frantic hyperactivity not seen with CT-921. At equivalent analgesic doses, THC was much less in CT-921 than in CT-928 suggesting interactions with components other than THC influenced the analgesia. At equivalent analgesic doses, efficacy-to-adverse effect profile for CT-928 was worse than for CT-921.
Conclusion: Both extracts relieved neuropathic pain; however, CT-921 had a better efficacy-to-adverse effect profile, a rational basis for prioritizing cultivars for future clinical evaluation.
中文翻译：
大麻提取物 CT-921 在神经性疼痛模型中具有高效的副作用。
背景：大麻合法化鼓励开发特定品种来治疗神经性疼痛等疾病。由于品种众多，在进行临床试验之前有必要优先提取提取物。
目的：比较两种独特的大麻品种（CT-921、CT-928）的提取物治疗小鼠坐骨神经收缩引起的神经性疼痛，并说明使用该动物模型确定未来试验的优先级。
方法：通过引起缩爪的阈值力测量疼痛严重程度。确定静脉注射品种和载体提取物的剂量-反应关系和时间进程。缓解异常性疼痛的剂量与降低的呼吸频率、温度和行为变化相关。
结果： 50% 和 95%（ED 50An和 ED 95An ）的有效镇痛剂量为15，CT-921 为 29 mg/kg，CT-928 为 0.9 和 4.7。在 ED 50An时，两种提取物的持续时间均为 120 分钟。在 ED 95An，给予 CT-928 显着降低呼吸频率，而 CT-921 则没有。CT-928 比 CT-921 降低温度更多。CT-928 产生了 CT-921 所没有的疯狂的多动症。在相同的镇痛剂量下，CT-921 中的 THC 远低于 CT-928，这表明与 THC 以外的成分的相互作用会影响镇痛。在相同的镇痛剂量下，CT-928 的疗效-不良反应曲线比 CT-921 差。
结论：两种提取物均能缓解神经性疼痛；然而，CT-921 具有更好的疗效-不良反应谱，这是为未来临床评估优先考虑栽培品种的合理基础。
更新日期：2020-08-17
Purpose: To compare extracts of two unique cannabis cultivars (CT-921, CT-928) for treatment of neuropathic pain induced by constriction of sciatic nerve in mice and to illustrate the use of this animal model to set priority for future trials.
Methods: Pain severity was measured by threshold force causing paw withdrawal. Dose–response relationships and time course were determined for intravenously injected extracts of cultivars and vehicle. The doses for allodynia relief were correlated with decreased respiratory rate, temperature and behavioral changes.
Results: Effective analgesic dose for 50 and 95% (ED50An and ED95An) was 15, and 29 mg/kg for CT-921 and 0.9 and 4.7 for CT-928. At ED50An, for both extracts, the duration was 120 min. At ED95An, administration of CT-928 significantly decreased respiratory rate while CT-921 did not. CT-928 decreased temperature more than CT-921. CT-928 produced frantic hyperactivity not seen with CT-921. At equivalent analgesic doses, THC was much less in CT-921 than in CT-928 suggesting interactions with components other than THC influenced the analgesia. At equivalent analgesic doses, efficacy-to-adverse effect profile for CT-928 was worse than for CT-921.
Conclusion: Both extracts relieved neuropathic pain; however, CT-921 had a better efficacy-to-adverse effect profile, a rational basis for prioritizing cultivars for future clinical evaluation.
中文翻译：
大麻提取物 CT-921 在神经性疼痛模型中具有高效的副作用。
背景：大麻合法化鼓励开发特定品种来治疗神经性疼痛等疾病。由于品种众多，在进行临床试验之前有必要优先提取提取物。
目的：比较两种独特的大麻品种（CT-921、CT-928）的提取物治疗小鼠坐骨神经收缩引起的神经性疼痛，并说明使用该动物模型确定未来试验的优先级。
方法：通过引起缩爪的阈值力测量疼痛严重程度。确定静脉注射品种和载体提取物的剂量-反应关系和时间进程。缓解异常性疼痛的剂量与降低的呼吸频率、温度和行为变化相关。
结果： 50% 和 95%（ED 50An和 ED 95An ）的有效镇痛剂量为15，CT-921 为 29 mg/kg，CT-928 为 0.9 和 4.7。在 ED 50An时，两种提取物的持续时间均为 120 分钟。在 ED 95An，给予 CT-928 显着降低呼吸频率，而 CT-921 则没有。CT-928 比 CT-921 降低温度更多。CT-928 产生了 CT-921 所没有的疯狂的多动症。在相同的镇痛剂量下，CT-921 中的 THC 远低于 CT-928，这表明与 THC 以外的成分的相互作用会影响镇痛。在相同的镇痛剂量下，CT-928 的疗效-不良反应曲线比 CT-921 差。
结论：两种提取物均能缓解神经性疼痛；然而，CT-921 具有更好的疗效-不良反应谱，这是为未来临床评估优先考虑栽培品种的合理基础。
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