Brierley Daniel I, Samuels James, Duncan Marnie, Whalley Benjamin J, Williams Claire M
School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
School of Chemistry, Food and Nutritional Sciences, and Pharmacy, University of Reading, Reading, UK.
Psychopharmacology (Berl). 2016 Jan;233(2):243-54. doi: 10.1007/s00213-015-4100-1. Epub 2015 Oct 6.
Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation.
This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours.
Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests.
CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box.
CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.
预期性恶心（AN）是化疗患者中一种难以控制的副作用。目前，药物治疗仅限于苯二氮䓬类抗焦虑药，其疗效有限，有显著的镇静作用且会导致依赖。非精神活性植物大麻素大麻二酚酸（CBDA）在临床前的预期性恶心模型中已显示出相当的疗效，然而确定其神经运动耐受性特征对于证明其临床研究的合理性至关重要。其食欲刺激特性的初步证据也需要详细研究。
本研究旨在评估CBDA在运动活动、运动协调性和肌肉力量测试中的耐受性，并评估其调节进食行为的能力。
对给予CBDA（0.05 - 5毫克/千克；口服）的雄性利斯特戴帽大鼠进行习惯化旷场实验（用于评估运动活动）、静态横梁实验和握力测试。另一项研究调查了这些CBDA剂量是否会调节正常进食行为。最后，在习惯化旷场实验中观察到的类似抗焦虑作用促使对5毫克/千克的CBDA进行测试，以评估其在非习惯化旷场实验、明暗箱实验和新奇抑制进食（NSF）实验中的抗焦虑样活性。
CBDA对任何神经运动耐受性测试的表现均无不良影响，然而在习惯化旷场实验中观察到了类似抗焦虑的行为。任何剂量的CBDA均未影响正常进食行为。CBDA（5毫克/千克）消除了5 - HT1AR拮抗剂WAY - 100,635诱导的NSF实验中进食潜伏期的延长，这表明其具有抗焦虑样作用，但对新奇旷场实验或明暗箱实验中的焦虑样行为没有影响。
CBDA耐受性良好，没有苯二氮䓬类药物的镇静副作用，证明其作为一种新型预期性恶心治疗方法进行临床研究是合理的。
