Pre-clinical evaluation of combined CBDA:THCA on nausea in veterinary medicine

几千年来，大麻一直被用来治疗恶心和呕吐。事实上，这种症状是第一个获得批准的医用大麻处方。大麻中的主要精神活性成分是四氢大麻二酚(THC)，另一种非精神药物成分是大麻二酚(CBD)，两者都具有抗恶心和止吐的特性。然而，我们的研究小组最近发现，THC的酸性前体THC-酸(THCA)和CBD的酸性前体CBD-酸(CBDA)在加热后比它们的产物具有更强的抗恶心作用。事实上，THCA是非精神药物，可能是比其精神药物产品更好的治疗方法。事实上，CBDA在减少恶心和呕吐方面的效力是CBD的1000倍，但没有精神运动作用。由于CBDA和THCA都存在于生大麻植物中(根据菌株的不同浓度)，本研究将确定这两种化合物的潜在协同作用，一种作用于5-HT1a受体(CBDA)，另一种作用于CB1受体(THCA可能在外围)，以减少恶心和呕吐，可能成为兽药。关于这些化合物的组合对恶心和呕吐的影响的研究很少。在这里，我们建议评估THCA：CBDA剂量的不同组合比任何一种单独使用更有效地减少恶心的潜力。我们还将确定THCA对恶心的影响是外周还是中枢调节的。这些实验的结果将为正在接受化疗的同伴动物提供潜在的新疗法的临床前评估。

Cannabis has been used to treat nausea and vomiting for thousands of years. Indeed, this symptom was the first to receive approval for medical marijuana prescriptions. The primary psychoactive ingredient in cannabis is tetrahydrocannabidiol (THC) and another non-psychotropic ingredient in cannabis is cannabidiol (CBD) which both have anti-nausea and anti-emetic properties. However, recently, our group has shown that the acidic precursors to THC, THC-acid (THCA), and to CBD, CBD-acid (CBDA), are much more potent anti-nausea agents then their products after heating. Indeed, THCA is non-psychotropic and may be a better treatment than its psychotropic product. Indeed, CBDA is 1000 times more potent in reducing nausea and vomiting than CBD, but has no psychomotor effects. Since CBDA and THCA are both present (at various concentrations depending upon strain) in the raw cannabis plant, the present research will determine the potential synergistic effects of these compounds, one that acts on 5-HT1A receptors (CBDA) and the other which acts on CB1 receptors (THCA possibly peripherally) to reduce nausea and vomiting for potential development as veterinary medicines. There has been very little research on the effects of combinations of these compounds on nausea and vomiting. Here we propose to evaluate the potential of various combinations of THCA:CBDA doses to more effectively reduce nausea than either agent on its own. We will also determine if the effects of THCA on nausea are peripherally or centrally mediated. The results of these experiments will provide pre-clinical evaluation of potential new therapies for companion animals undergoing chemotherapy treatment.